Summary
Antibiotics can interact directly with the immune system. This is a review of the immunomodulating effects of antibiotics. The Medline database on CD-ROM was searched for the years 1987 to 1994 using the following search string: “thesaurus explode antibiotics / all AND (thesaurus explode immune-system / drug effects ORthesaurus immune-tolerance / drug effects).” Aspects of the immune system studied were aspects of phagocyte functions: phagocytosis and killing, and chemotaxis and aspects of lymphocyte functions: lymphocyte proliferation, cytokine production, antibody production, delayed hypersensitivity and natural killer-cell activity. In order to quantify and to compare immunomodulatory properties of antibiotics we calculated an “immune index,” defined as: number of positive statements — number of negative statements/total number of statements. Concerning phagocytosis, positive effects were observed for cefodizime, imipenem, cefoxitin, amphotericin B and clindamycin and negative effects for erythromycin, roxithromycin, cefotaxime, tetracycline, amplicillin and gentamicin. Clindamycin, cefoxitin and imipenem induce enhancement of chemotaxis, whereas cefotaxime, rifampicin and teicoplanin decrease chemotaxis. Regarding lymphocyte proliferation, cefodizime has the strongest stimulating effect, whereas tetracycline has the strongest negative effect. Except for erythromycin and amphotericin B the number of statements reported is too small to be conclusive for the interpretation of effects on cytokine production. Erythromycin and amphotericin B appear to stimulate cytokine production. As to antibody production, cefodizime has the strongest positive effect, whereas josamycin, rifampicin and tetracycline have marked negative effects. For delayed hypersensitivity and the natural killer-cell activity the number of statements is too small for any single antibiotic to be conclusive. There are three markedly immuno-enhancing antibiotics (imipenem, cefodizime and clindamycin) and eight markedly immuno-depressing antibiotics (erythromycin, roxithromycin, cefotaxime, tetracycline, rifampicin, gentamicin, teicoplanin and ampicillin).
Zusammenfassung
Antibiotika können direkt mit dem Immunsystem in Wechselwirkung treten. Im Folgenden geben wir eine Übersicht über immunmodulierende Wirkungen von Antibiotika. Medline Datenbasen auf CD-ROM für die Jahre 1987–1994 mit den Stichworten “thesaurus explode antibiotics / all AND (thesaurus explode immune-system/ drug effects ORthesaurus immune-tolerance / drug effects)” wurden befragt. Die immunologischen Studien betrafen Aspekte der Phagozytenfunktionen: Phagozytose und Abtötung sowie Chemotaxis und Aspekte der Lymphozytenfunktion, Lymphozytenproliferation, Zytokinproduktion, Antikörperbildung, Überempfind-lichkeitsreaktion vom verzögerten Typ und natürliche Killerzellaktivität. Um immunmodulierende Eigenschaften von Antibiotika quantifizierbar und vergleichbar zu machen, wurde ein wie folgt definierter “Immunindex” berechnet: Zahl positive Aussagen — Zahl negativer Aussagen/Gesamtaussagen. Positive Wirkungen auf die Phagozyten wurden mit Cefodizim, Imipenem, Cefoxitin, Amphotericin B und Clindamycin gemacht. Bei Erythromycin, Roxithromycin, Cefotaxim, Tetracyklin, Ampicillin und Gentamicin wurden negative Effekte beobachtet. Clindamycin, Cefoxitin und Imipenem induzieren eine Verstärkung der Chemotaxis. Auf die Lymphozyten-proliferation hat Cefodizim den stärksten Stimulationseffekt, Tetrazyklin hat den stärksten negativen Effekt. Die Wirkung auf Zytokinproduktion kann nur für Erythromycin und Amphotericin B beurteilt werden, bei allen anderen Substanzen reichen die Daten hierfür nicht aus. Erythromycin und Amphotericin B führen offensichtlich zu einer Stimulation der Zytokinproduktion. Auf die Antikörperbildung hat Cefodizim die stärkste positive Wirkung, deutlich negative Effekte wurden mit Josamycin, Rifampicin und Tetrazyklin beobachtet. Für die verschiedenen Antibiotika liegen nicht genügend Studien zur Überempfindlichkeitsreaktion vom verzögerten Typ oder zur Natural Killer Cell Aktivität vor. Drei der Antibiotika haben ausgeprägte fördernde Wirkung auf das Immunsystem (Imipenem, Cefodizim, Clindamycin), acht haben ausgeprägt immunsuppressive Wirkung (Erythromycin, Roxithromycin, Cefotaxim, Tetrazyklin, Rifampicin, Gentamicin, Teicoplanin und Ampicillin).
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References
Hauser, W. E., Remington, J. S. Effect of antibiotics on the immune response. Am. J. Med. 72 (1982) 711–716.
Korzeniowski, O. M. Effects of antibiotics on the mammalian immune system. Infect. Dis. Clin. North. Am. 3 (1989) 469–478.
van den Broek, J. Antimicrobial drugs, microorganisms, and phagocytes. Rev. Infect. Dis. 11 (1989) 213–245.
Gemmell, C. G. Antibiotics and neutrophil function — potential immunomodulating activities. J. Antimicrob. Chemother. 31 (Suppl. B) (1993) 23–33.
Labro, M. T., el-Benna, J. Effects of anti-infectious agents on polymorphonuclear neutrophils. Eur. J. Clin. Microbiol. Infect. Dis. 10 (1991) 124–131.
Milatovic, D. Antibiotics and phagocytosis. Eur. J. Clin. Microbiol. 2 (1983) 414–425.
Ringoir, S. The “infection equation.” Infection 20 (Suppl. 1) (1992) S75-S77.
Carevic, O., Djokic, S. Comparative studies on the effects of erythromycin A and azithromycin upon extracellular release of lysosomal enzymes in inflammatory processes. Agents Actions 25 (1988) 124–131.
Corrales, I., Aguilar, L., Mato, R., Frias, J., Prieto, J. Immunomodulatory effect of cefminox. [Letter] J. Antimicrob. Chemother. 33 (1994) 372–374.
Sheng, F. C., Freischlag, J., Bacstrom, B., Kelly, D., Busuttil, R. W. The effects ofin vivo antibiotics on neutrophil (PMN) activity in rabbits with peritonitis. J. Surg. Res. 43 (1987) 239–245.
Paape, M. J., Nickerson, S. C., Ziv, G. In vivo effects of chloramphenicol, tetracycline, and gentamicin on bovine neutrophil function and morphologic features. Am. J. Vet. Res. 51 (1990) 1055–1061.
Chang, F. Y., Shaio, M. F. In vitro effect of actinomycin D on human neutrophil function. Microbiol. Immunol. 34 (1990) 311–321.
Paape, M. J., Miller, R. H., Ziv, G. Pharmacologic enhancement or suppression of phagocytosis by bovine neutrophils. Am. J. Vet. Res. 52 (1991) 363–366.
Fromtling, R., Abruzzo, A., G. K., Turnbull, T. A., Giltinan, D. M., Capizzi, T. P. Use of chemiluminescence to evaluate the influence of antifungal agents on immune cell function. Ann. N. Y. Acad. Sci. 544 (1988) 270–283.
Gunther, M. R., Mao, J., Cohen, M. S. Oxidant-scavenging activities of ampicillin and sulbactam and their effects on neutrophil functions. Antimicrob. Agents Chemother. 37 (1993) 950–956.
Ottonello, L., Dallegri, F., Dapino, P., Pastorino, G., Sacchetti, C. Cytoprotection against neutrophil-delivered oxidant attack by antibiotics. Biochem. Pharmacol. 42 (1991) 2317–2321.
Briheim, G., Dahlgren, C. Influence of antibiotics on formylmethionyl-leucyl-phenylalanine-induced leukocyte chemiluminescence. Antimicrob. Agents Chemother. 31 (1987) 763–767.
Lintner, T. J., Eberhart, R. J. Effects of bovine mammary secretion during the early nonlactating period and antibiotics on polymorphonuclear neutrophil function and morphology. Am. J. Vet. Res. 51 (1990) 524–532.
Abruzzo, G. K., Fromtling, R. A., Turnbull, T. A., Giltinan, D. M. Effects of bifonazole, fluconazole, itraconazole, and terbinafine on the chemiluminescence response of immune cells. J. Antimicrob. Chemother. 20 (1987) 61–68.
Nielsen, H. Antibiotics and human monocyte function. II. Phagocytosis and oxidative metabolism. APMIS 97 (1989) 447–451.
Ford, L. C., Nilsson, J. D., Hammill, H. A. Effects of cefotetan disodium, cefoxitin, cefazolin, and cefotaximein vitro on polymorphonuclear leukocytes from patients with leukopenia and severe pelvic inflammatory disease. Am. J. Obstet. Gynecol. 158 (1988) 744–745.
Noess, A., Hauge, B., Solberg, C. O. Effects of clindamycin and cefuroxime on leukocyte membrane receptors and function. Chemotherapy 35 (1989) 193–199.
Olver, S. D., Price, P., Karthigasu, K. T. Potentiation of murine cytomegalovirus pneumonitis by antibiotics in clinical use. J. Antimicrob. Chemother. 27 (1991) 81–94.
Paape, M. J., Miller, R. H., Ziv, G. Effects of florfenicol, chloramphenicol, and thiamphenicol on phagocytosis, chemiluminescence, and morphology of bovine polymorphonuclear neutrophil leukocytes. J. Dairy. Sci. 73 (1990) 1734–1744.
Hand, W. L., Hand, D. L., King-Thompson, N. L. Antibiotic inhibition of the respiratory burst response in human polymorphonuclear leukocytes. Antimicrob. Agents Chemother. 34 (1990) 863–870.
Van der Auwera, P., Husson, M., Fruhling, J. Influence of various antibiotics on phagocytosis ofStaphylococcus aureus by human polymorphonuclear leucocytes. J. Antimicrob. Chemother. 20 (1987) 399–404.
Osawa, N. Use of cycloheximide on intracellular growth ofMycobacterium leprae in cultured murine macrophages. Kitasato. Arch. Exp. Med. 64 (1991) 205–212.
Kenny, M. T., Torney, H. L., Balistreri, F. J. Comparative effect of the naphthalenic ansamycins rifamycin SV, rifampin and cyclopentylrifampicin on murine neutrophil function. Int. J. Immunopharmacol. 11 (1989) 915–920.
Miyatake, H., Suzuki, K., Taki, F., Takagi, K., Satake, T. Effect of erythromycin on bronchial hyperresponsiveness in patients with bronchial asthma. Arzneimittelforschung 41 (1991) 552–556.
Anderson, R. Erythromycin and roxithromycin potentiate human neutrophil locomotionin vitro by inhibition of leukoattractant-activated superoxide generation and autooxidation. J. Infect. Dis. 159 (1989) 966–973.
Carlone, N. A., Cufini, A. M., Tullio, V., Sassella, D. Comparative effects of roxithromycin and erythromycin on cellular immune functionsin vitro. 2. Chemotaxis and phagocytosis of 3H-Staphylococcus aureus by human macrophages. Microbios 58 (1989) 17–25.
Bretzlaff, K. N., Neff-Davis, C. A., Ott, R. S., Koritz, G. D., Gustafsson, B. K., Davis, L.E. Florfenicol in non-lactating dairy cows: pharmacokinetics, binding to plasma proteins, and effects on phagocytosis by blood neutrophils. J. Vet. Pharmacol. Ther. 10 (1987) 233–240.
Ogle, J. D., Noel, J. G., Sramkoski, R. M., Ogle, C. K., Alexander, J. W. Effect of antibiotics on CR1 receptor levels of human neutrophils and on the binding and phagocytosis of opsonized polystyrene microspheres by these leucocytes. Burns 15 (1989) 141–144.
Gemmell, C. G. Macrolides and host defences to respiratory tract pathogens. J. Hosp. Infect. 19 (Suppl. A) (1991) 11–19.
Labro, M. T., el-Benna, J., Babin-Chevaye, C. Comparison of thein vitro effect of several macrolides on the oxidative burst of human neutrophils. J. Antimicrob. Chemother. 24 (1989) 561–572.
Van der Auwera, P., Bonnet, M., Husson, M. Influence of teicoplanin and vancomycin on degranulation by polymorphonuclear leucocytes stimulated by various agonists: anin vitro study. J. Antimicrob. Chemother. 26 (1990) 683–688.
Capodicasa, E., Scaringi, L., Rosati, E., De Bellis, F., Sbaraglia, G., Marconi, P., Del Favero, A. In-vitro effects of teicoplanin, teicoplanin derivative MDL 62211 and vancomycin on human polymorphonuclear cell function. J. Antimicrob. Chemother. 27 (1991) 619–626.
Maderazo, E. G., Breaux, S. P., Woronick, C. L., Quintiliani, R., Nightingale, C. H. High teicoplanin uptake by human neutrophils. Chemotherapy 34 (1988) 248–255.
Gabler, W. L., Creamer, H. R. Suppression of human neutrophil functions by tetracyclines. J. Periodontal. Res. 26 (1991) 52–58.
Lintner, T. J., Eberhart, R. J. Effects of antibiotics on phagocyte recruitment, function, and morphology in the bovine mammary gland during the early nonlactating period. Am. J. Vet. Res. 51 (1990) 533–542.
Gialdroni-Grassi, G., Bersani, C., Uccelli, M., Fietta, A. Influence of cefoperazone on neutrophil functions in volunteers. [Letter] Eur. J. Clin. Microbiol. 6 (1987) 327–328.
Auteri, A., Pasqui, A. L., Bruni, F., Saletti, M., Mazza, S., Di Renzo, M., Maggiore, D., Di Perri, T. Effect of cefodizime (HR 221) on immunological defects induced by surgical stress. Drugs. Exp. Clin. Res. 17 (1991) 555–561.
Tawfik, A. F. Effects of vancomycin, teicoplanin, daptomycin and coumermycin on normal immune capabilities. J. Chemother. 3 (1991) 226–231.
Preus, H., Tollefsen, T., Morland, B. Effects of tetracycline on human monocyte phagocytosis and lymphocyte proliferation. Acta. Odontol. Scand. 45 (1987) 297–302.
Bonnet, M., Van der Auwera, P. In vitro andin vivo intraleukocytic accumulation of azithromycin (CP-62, 993) and its influence onex vivo leukocyte chemiluminescence. Antimicrob. Agents Chemother. 36 (1992) 1302–1309.
Limbert, M., Mullner, H., Shah, P. M. Influence of cefodizime on the reagibility of human leukocytes. Infection 20 (Suppl. 1) (1992) S48-S50.
Vanholder, R., Dagrosa, E. E., Van Landschoot, N., Waterloos, M. A., Ringoir, S. M. Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole. Nephron. 63 (1993) 65–72.
Nelson, S., Summer, W. R., Terry, P. B., Warr, G. A., Jakab, G. J. Erythromycin-induced suppression of pulmonary antibacterial defenses. A potential mechanism of superinfection in the lung. Am. Rev. Respir. Dis. 136 (1987) 1207–1212.
Bersani, C., Bertoletti, R., Colombo, M. L., Merlini, C., Uccelli, M., Fietta, A., Gialdroni-Grassi, G. In vitro andex vivo influence of rifamycins on human phagocytes. Chemioterapia 6 (1987) 420–425.
Pascual, A., Martinez-Martinez, L., Aragon, J., Perea, E. J. Effect of amoxycillin and clavulanic acid, alone and in combination, on human polymorphonuclear leukocyte function againstStaphylococcus aureus. Eur. J. Clin. Microbiol. Infect. Dis. 8 (1989) 277–281.
Pallister, C. J., Johnson, E. M., Warnock, D. W., Elliot, P. J., Reeves, D. F. In-vitro effects of liposome-encapsulated amphotericin B (AmBisome) and amphotericin B-deoxycholate (Fungizone) on the phagocytic and candidacidal function of human polymorphonuclear leucocytes. J. Antimicrob. Chemother. 30 (1992) 313–320.
Van der Auwera P., Meunier, F. In-vitro effects of cilofungin (LY 121019), amphotericin B and amphotericin B-deoxycholate on human polymorphonuclear leucocytes. J. Antimicrob. Chemother. 24 (1989) 747–763.
Yasui, K., Masuda, M., Matsuoka, T., Yamazaki, M., Komiyama, A., Akabane, T., Murata, K. Miconazole and amphotericin B alter polymorphonuclear leukocyte functions and membrane fluidity in similar fashions. Antimicrob. Agents Chemother. 32 (1988) 1864–1868.
Pascual, A., Lopez-Lopez, G., Aragon, J., Perea, E. J. Effect of azithromycin, roxithromycin and erythromycin on human polymorphonuclear leukocyte function againstStaphylococcus aureus. Chemotherapy 36 (1990) 422–427.
Labro, M. T., el-Benna, J., Charlier, N., Abdelghaffar, H., Hakim, J. Cefdinir (CI-983), a new oral amino-2-thiazolyl cephalosporin, inhibits human neutrophil myeloperoxidase in the extracellular medium but not the phagolysosome. J. Immunol. 152 (1994) 2447–2455.
Shaio, M. F., Chang, F. Y. Influence of cefodizime on chemotaxis and the respiratory burst in neutrophils from diabetics. J. Antimicrob. Chemother. 26 (1990) 55–59.
Grochla, I., Ko, H. L., Beuth, J., Roszkowski, K., Roszkowski, W., Pulverer, G. Effects of beta-lactam antibiotics imipenem/cilastatin and cefodizime on cellular and humoral immune responses in BALB/c-mice. Int. J. Med. Microbiol. 274 (1990) 250–258.
Meroni, P. L., Capsoni, F., Borghi, M. O., Barcellini, W., Minonzio, F., Ongari, A. M., Fain, C., Hu, C., Brambilla, G., Pettenati, C., Zanussi, C. Immunopharmacological activity of cefodizime in young and elderly subjects:in vitro andex vivo studies. Infection 20 (Suppl. 1) (1992) S61-S63.
Tullio, V., Cuffini, A. M., Fazari, S., Carlone, N. A. Cefonicid potentiation of human macrophage activity. Microbiologica 15 (1992) 219–226.
Schubert, S., Ullmann, U. Influence of cefpodoxime on selected immunological functions and bacterial pathogenicity factorsin vitro. Int. J. Med. Microbiol. 275 (1991) 233–240.
Braga, P. C., Piatti, G., Dal-Sasso, M., Maci, S., Blasi, F. Thein vitro effects of ceftibuten on the host defense mechanism. Chemotherapy 40 (1994) 37–41.
Leonardi, M. S., Garotta, F., Berlinghieri, M. C., Bonina, L., Mastroeni, P. Influence of ceftizoxime on the immune system. Chemioterapia 6 (1987) 417–419.
Labro, M. T., Babin-Chevaye, C., Pochet, I., Hakim, J. Interaction of ceftriaxone with human polymorphonuclear neutrophil function. J. Antimicrob. Chemother. 20 (1987) 849–855.
Moran, F. J., Puente, L. F., Perez-Giraldo, C., Hurtado, C., Blanco, M. T., Gomez-Garcia, A. C. Effects of cefpirome in comparison with cefuroxime against human polymorphonuclear leucocytesin vitro. J. Antimicrob. Chemother. 33 (1994) 57–62.
Baker, P. J., Wilson, M. E. Effect of clindamycin on neutrophil killing of gram-negative periodontal bacteria. Antimicrob. Agents Chemother. 32 (1988) 1521–1527.
Sahu, A., Saha, K., Banerjee, N. R., Sehgal, V. N., Jagga, C. R. Effect of anti-leprosy drugs on superoxide anion production by rat peritoneal macrophage with special reference to light exposed clofazimine. Int. J. Immunopharmacol. 13 (1991) 419–428.
Dahlgren, C., Norberg, B., Eriksson, S. Doxycycline effects on the adherence of polymorphonuclear leukocytes to an albumin-coated glass surface. Scand. J. Infect. Dis. 19 (1987) 545–549.
Dumas, R., Brouland, J. P., Tedone, R., Descotes, J. Influence of macrolide antibiotics on the chemiluminescence of zymosan-activated human neutrophils. Chemotherapy 36 (1990) 381–384.
Bacci, P., Grossi, A., Vannucchi, A. M., Rafanelli, D., Casini, A., De Luca, M. Effects of miocamycin and erythromycin on polymorphonuclear cell function. J. Chemother. 4 (1992) 268–270.
Naess, A., Flo, R. W., Solberg, C. O. Effect of fusidic acid on migration and chemiluminescence of polymorphonuclear leukocytes. Eur. J. Clin. Microbiol. Infect. Dis. 9 (1990) 42–44.
Kharazmi, A., Nielsen, H. Fusidic acid and human phagocyte function. [Letter] J. Antimicrob. Chemother. 22 (1988) 262–263.
Easmon, C. S. Interaction of meropenem with humoral and phagocytic defences. J. Antimicrob. Chemother. 24 (Suppl. A) (1989) 259–264.
Rodriguez, A. B., Pariente, J., Prieto, J., Barriga, C. Effects of cefmetazol, cefoxitin and imipenem on polymorphonuclear leukocytes. Gen. Pharmacol. 18 (1987) 613–615.
Kazmierczak, A., Pechinot, A., Siebor, E., Cordin, X., Labia, R. Sulbactam: secondary mechanisms of action. Diagn. Microbiol. Infect. Dis. 12 (4 Suppl.) (1989) 139S-146S.
Kumae, T., Saburi, Y., Nasu, M., Misumi, J., Kawata, N. Effects of cefbuperazone on the chemiluminescence of human neutrophils. Chemotherapy 35 (1989) 260–266.
Labro, M. T. Cefodizime as a biological response modifier: a review of itsin-vivo, ex-vivo andin-vitro immunomodulatory properties. J. Antimicrob. Chemother. 26 (Suppl. C) (1990) 37–47.
Vanholder, R., Van Landschoot, N., Dagrosa, E., Ringoir, S. Cefodizime: a new cephalosporin with apparent immune-stimulating properties in chronic renal failure. Nephrol. Dial. Transplant. 3 (1988) 221–224.
Scaglione, F., Ferrara, F., Duganani, S., Demartini, G., Triscari, F., Fraschini, F. Immunostimulation by clarithromycin in healthy volunteers and chronic bronchitis patients. J. Chemother. 5 (1993) 228–232.
Kitz, D. J., Neuman, H. R., Little, J. R. Clindamycin enhances murine delayed-type hypersensitivity and anti-candidal activity. J. Antimicrob. Chemother. 23 (1989) 721–728.
Astry, C. L., Nelson, S., Karam, G. H., Summer, W. R. Interactions of clindamycin with antibacterial defenses of the lung. Am. Rev. Respir. Dis. 135 (1987) 1015–1019.
Santos, J. I., Arbo, A., Pavia, N. In vitro andin vivo effects of clindamycin on polymorphonuclear leukocyte function. Clin. Ther. 14 (1992) 578–594.
Bassaris, H. P., Lianou, P. E., Skoutelis, A. T., Papavassiliou, J. T. In-vivo effects of clindamycin on polymorphonuclear leucocyte phagocytosis and killing of gram-negative organisms. J. Antimicrob. Chemother. 19 (1987) 467–473.
Nunez, R. M., Rodriguez, A. B., Barriga, C., De-la-Fuente, M. In vitro andin vivo effects of imipenem on phagocytic activity of murine peritoneal macrophages. APMIS 97 (1989) 879–886.
Pedrera, M. I., Perez, F., Rodriguez, A. B., Barriga, C. Stimulation of phagocytosis againstStaphylococcus aureus by teicoplanin and vancomycin. Rev. Esp. Fisiol. 49 (1993) 231–234.
Labro, M. T. Immunological evaluation of cefodizime: a unique molecule among cephalosporins. Infection 20 (Suppl. 1) (1992) S45-S47.
Gialdroni-Grassi, G., Shah, P. M. Cefodizime host-defence enhancement: considerations of dose-response relationships in healthy volunteers. Infection 20 (Suppl. 1) (1992) S51-S53.
Fietta, A., Bersani, C., Bertoletti, R., Grassi, F. M., Grassi, G. G. In vitro andex vivo enhancement of nonspecific phagocytosis by cefodizime. Chemotherapy 34 (1988) 430–436.
Vanholder, R., Ringoir, S. Cefodizime: enhancement of depressed phagocytosis-associated respiratory burst activity in chronic uremic patients. Infection 20 (Suppl. 1) (1992) S71-S74.
Dammacco, F., Benvestito, S. Effects of cefodizime on non-specific immune functions in patients with multiple myeloma. Infection 20 (Suppl. 1) (1992) S64-S66.
Ueta, E., Yoneda, K., Yamamoto, T., Osaki, T. Upregulatory effects of cefpimizole natrium on human leukocytes. Int. J. Immunopharmacol. 14 (1992) 877–885.
Cuffini, A. M., Carlone, N. A., Xerri, L., Pizzoglio, M. F. Synergy of ceftazidime and human macrophages on phagocytosis and killing ofStaphylococcus aureus andPseudomonas aeruginosa. J. Antimicrob. Chemother. 20 (1987) 261–271.
Fraschini, F., Scaglione, F., Ferrara, F., Dugnani, S., Zecca, L. Effects of lincomycin on the immune system. Chemotherapy 33 (1987) 61–67.
Fraschini, F., Scaglione, F., Ferrara, F., Dugnani, S., Falchi, M., Cattaneo, G. Miokamycin and leukocyte activity in man. Chemotherapy 35 (1989) 289–295.
Beccari, T., Mazzolla, R., Constanzi, E., Datti, A., Barluzzi, R., Bistoni, F., Orlacchio, A. Amphotericin B stimulates secretion of beta-hexosaminidase from mouse adherent spleen cells. Biochem. Int. 24 (1991) 235–241.
Aslanzadeh, J., Mormol, J. S., Little, J. R. Anticryptococcal activity of amphotericin B-stimulated macrophages. Immunopharmacol. Immunotoxicol. 13 (1991) 465–483.
Wilson, E., Thorson, L., Speert, D. P. Enhancement of macrophage superoxide anion production by amphotericin B. Antimicrob. Agents Chemother. 35 (1991) 796–800.
Okai, Y., Ishizaka, S. A possible immunomodulating activity of arbekacin (ABK), a newly synthesized antibiotic against methicillin-resistantStaphylococcus aureus (MRSA). Int. J. Immunopharmacol. 16 (1994) 321–327.
Rodriguez, A. B., Sanchez, C., Barriga, C. Effect of aztreonam upon human polymorphonuclear leukocyte functions. Comp. Immunol. Microbiol. Infect. Dis. 15 (1992) 131–136.
Adinolfi, L. E., Utili, R., Dilillo, M., Tripodi, M. F., Attanasio, V., Ruggiero, G. Intracellular activity of cefamandole and aztreonam against phagocytosedEscherichia coli andStaphylococcus aureus. J. Antimicrob. Chemother. 24 (1989) 927–935.
Lingaas, E., Midtvedt, T. The influence of cefoperazone, cefotaxime, ceftazidime and aztreonam on phagocytosis by human neutrophilsin vitro. J. Antimicrob. Chemother. 23 (1989) 701–710.
Velluti, G., Garuti, G. C., Bonucchi, M. E., Gilioli, F., Capelli, O., Rovatti, E., Covi, M. Activity of aztreonam in pneumology, part 2: Influence on phagocytosis and intracellular killing of human alveolar macrophages. J. Chemother. 6 (1994) 44–49.
Scheffer, J., Knoller, J., Cullmann, W., Konig, W. Effects of cefaclor, cefetamet and Ro 40-6890 on inflammatory responses of human granulocytes. J. Antimicrob. Chemother. 30 (1992) 57–66.
Oishi, K., Matsumoto, K., Yamamoto, M., Morito, T., Yoshida, T. Stimulatory effect of cefodizime on macrophage-mediated phagocytosis. J. Antibiot. Tokyo 42 (1989) 989–992.
Labro, M. T., Amit, N., Babin-Chevaye, C., Hakim, J. Cefodizime (HR 221) potentiation of human neutrophil oxygen-independent bactericidal activity. J. Antimicrob. Chemother. 19 (1987) 331–341.
Cuffini, A. M., Tullio, V., Fazari, S., Paizis, G., Carlone, N. A. The effects of sub-MICs of cefonicid on the interaction of human macrophages withKlebsiella pneumoniae. [Letter] J. Antimicrob. Chemother. 28 (1991) 933–935.
Korting, H. C., Seitz, R., Kreller, W. Influence of various concentrations of cefotiam and ceftizoxime on the phagocytosis of gonococci by polymorphonuclear granulocytes. Arzneimittelforschung 39 (1989) 428–431.
Rodriguez, A. B., Barriga, C., de la Fuente, M. In vitro effect of cefoxitin on phagocytic function and antibody-dependent cellular cytotoxicity in human neutrophils. Comp. Immunol. Microbiol. Infect. Dis. 16 (1993) 37–50.
Roszkowski, K., Beuth, J., Ko, H. L., Peters, G., Pulverer, G. Comparative study on the macrolides erythromycin and clarithromycin: antibacterial activity and influence on immune responses. Int. J. Med. Microbiol. 273 (1990) 518–530.
Hand, W. L., Hand, D. L. Interactions of dirithromycin with human polymorphonuclear leukocytes. Antimicrob. Agents Chemother. 37 (1993) 2557–2562.
Naess, A., Solberg, C. O. Effects of two macrolide antibiotics on human leukocyte membrane receptors and functions. APMIS 96 (1988) 503–508.
Jacob, J. Linear gramicidin activates neutrophil functions and the activation is blocked by chemotactic peptide receptor antagonist. FEBS. Lett. 231 (1988) 139–142.
Rodriguez, A. B., Barriga, C., de la Fuente, M. Phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophils in the presence of N-formimidoyl thienamycin. Agents Actions 31 (1990) 86–95.
Cuffini, A. M., Tullio, V., Allocco, A., Fazari, S., Giachino, F., Carlone, N. A. EnhancedStaphylococcus aureus susceptibility to immunodefences induced by sub-inhibitory and bactericidal concentrations of imipenem. J. Antimicrob. Chemother. 31 (1993) 559–568.
Capelli, A., Capelli, O., Azzolini, L., Richeldi, L., Prandi, E., Velluti, G. Activities of human alveolar macrophages (HAMs). Note 1: observations on phagocytosis and bacterial killing in the presence of miocamycin. Chemioterapia 7 (1988) 89–95.
Santos, J. I., Arbo, A. Thein vitro effect of sulbactam on polymorphonuclear leukocyte function. Diagn. Microbiol. Infect. Dis. 12 (1989) 147S-152S.
Oda, H., Kadota, J., Kohno, S., Hara, K. Erythromycin inhibits neutrophil chemotaxis in bronchoalveoli of diffuse panbronchiolitis. Chest 106 (1994) 1116–1123.
Kenny, M. T., Balistreri, F. J., Torney, H. L. Beta-lactam antibiotic modulation of murine neutrophil cytokinesis. Immunopharmacol. Immunotoxicol. 14 (1992) 797–811.
Van der Auwera, P., Husson, M. Influence of rifampicin and ansamycin on motility and adherence of human neutrophils studiedin vitro. J. Antimicrob. Chemother. 24 (1989) 347–353.
Burgaleta, C., Moreno, T. Effect of beta-lactams and aminoglycosides on human polymorphonuclear leucocytes. J. Antimicrob. Chemother. 20 (1987) 529–535.
Van der Auwera, P., Husson, M. Influence of antibiotics on motility and adherence of human neutrophils studiedin vitro. Drugs Exp. Clin. Res. 15 (1989) 211–218.
Aho, P., Mannisto, P. T. Effects of two erythromycins, doxycycline and phenoxymethylpenicillin on human leucocyte chemotaxisin vitro. J. Antimicrob. Chemother. 21 (Suppl. D) (1988) 29–32.
Gabler, W. L., Smith, J., Tsukuda, N. Doxycycline reduction of F-actin content of human neutrophils and fibroblasts. Inflammation 18 (1994) 107–118.
Yousif, M. A., Hay, R. J. Leucocyte chemotaxis to mycetoma agents — the effect of the antifungal drugs griseofulvin and ketoconazole. Trans. R. Soc. Trop. Med. Hyg. 81 (1987) 319–321.
Roques, C., Frayret, M. N., Luc, J., Michel, G., Perruchet, A. M., Cauquil, J., Levy, D. Effect of anin vivo immunostimulant treatment on PMN functions: interactions with antibioticsin vitro. Int. J. Immunopharmacol. 13 (1991) 1051–1057.
Ueyama, Y., Misaki, M., Ishihara, Y., Matsumura, T. Effects of antibiotics on human polymorphonuclear leukocyte chemotaxisin vitro. Br. J. Oral. Maxillofac. Surg. 32 (1994) 96–99.
Pycock, J. F., Allen, W. E., Porter, D. J., Boyd, E. H. The effect of various antibacterial preparations on thein vitro morphology and chemotactic response of equine neutrophils. J. Vet. Pharmacol. Ther. 11 (1988) 191–196.
Torre, D., Broggini, M., Rossi, S., Sampietro, C., Botta, V. Effect of rokitamycin on human polymorphonuclear leukocyte chemotaxis. Int. J. Tissue. React. 11 (1989) 27–29.
Eda, R., Townley, R. G., Hopp, R. J. Effect of terfenadine on human eosinophil and neutrophil chemotactic response and generation of superoxide. Ann. Allergy 73 (1994) 154–160.
Gabler, W. L., Tsukuda, N. The influence of divalent cations and doxycycline on iodoacetamide-inhibitable leukocyte adherence. Res. Commun. Chem. Pathol. Pharmacol. 74 (1991) 131–140.
Nielsen, H. Antibiotics and human monocyte function. I. Chemotaxis. Acta. Pathol. Microbiol. Immunol. Scand. B. 95 (1987) 293–296.
Torre, D., Broggini, M., Botta, V., Sampietro, C., Busarello, R., Garberi, C. In vitro andex vivo effects of recent and new macrolide antibiotics on chemotaxis of human polymorphonuclear leukocytes. J. Chemother. 3 (1991) 236–239.
Hojo, M., Fujita, I., Hamasaki, Y., Miyazaki, M., Miyazaki, S. Erythromycin does not directly affect neutrophil functions. Chest 105 (1994) 520–523.
Goya, T., Torisu, M., Doi, F., Yoshida, T. Effects of granulocyte colony stimulating factor and monobactam antibiotics (aztreonam) on neutrophil functions in sepsis. Clin. Immunol. Immunopathol. 69 (1993) 278–284.
Moraes, J. R., Moraes, F. R., Bechara, G. H. Participation of macrophages in chloramphenicol-potentiated carrageenin-induced peritonitis in rats. Braz. J. Med. Biol. Res. 26 (1993) 497–507.
Skoutelis, A. T., Lianou, P. E., Bassaris, H. P. In vivo potentiation of polymorphonuclear leukocyte chemotaxis by clindamycin. Infection 21 (1993) 321–323.
Rodriguez, A. B., Barriga, C., de la Fuente, M. Mechanisms of action involved in the chemoattractant activity of three beta-lactam antibiotics upon human neutrophils. Biochem. Pharmacol. 41 (1991) 931–936.
Pulverer, G. Effects of cefodizime and cefotaxime on cellular and humoral immune responses. Infection 20 Suppl. 1 (1992) S41-S44.
Metcalf, J. F., Wilson, G. B. Use of mitogen-induced lymphocyte transformation to assess toxicity of aminoglycosides. J. Environ. Pathol. Toxicol. Oncol. 7 (1987) 27–37.
Schindler, J. J., Warren, R. P., Allen, S. D., Jackson, M. K. Immunological effects of amphotericin B and liposomal amphotericin B on splenocytes from immune-normal and immune-compromised mice. Antimicrob. Agents Chemother. 37 (1993) 2716–2721.
Heinle, S., Stunkel, K., Zahner, H., Drautz, H., Bessler, W. G. Immunosuppressive effects of the macrolide antibiotic bafilomycin towards lymphocytes and lymphoid cell lines. Arzneimittelforschung 38 (1988) 1130–1133.
Rouveix, B., Groult, F., Levacher, M. Beta-lactam antibiotics and human lymphocyte function: thein vitro effect on blastogenesis, lymphokine production and suppressor cell functions. Int. J. Immunopharmacol. 9 (1987) 567–575.
Ibrahim, M. S., Maged, Z. A., Haron, A., Khalil, R. Y., Attallah, A. M. Antibiotics and immunity: effects of antibiotics on natural killer, antibody dependent cell-mediated cytotoxicity and antibody production. Chemioterapia 6 (1987) 426–430.
Takeshita, K., Yamagishi, I., Harada, M., Otomo, S., Nakagawa, T., Mizushima, Y. Immunological and anti-inflammatory effects of clarithromycin: inhibition of interleukin 1 production of murine peritoneal macrophages. Drugs. Exp. Clin. Res. 15 (1989) 527–533.
Keicho, N., Kudoh, S., Yotsumoto, H., Akagawa, K. S. Antilymphocytic activity of erythromycin distinct from that of FK506 or cyclosporin A. J. Antibiot. Tokyo 46 (1993) 1406–1413.
Morikawa, K., Oseko, F., Morikawa, S. Immunomodulatory effect of fosfomycin on human B-lymphocyte function. Antimicrob. Agents Chemother. 37 (1993) 270–275.
Ingham, E. Modulation of the proliferative response of murine thymocytes stimulated by IL-1, and enhancement of IL-1 beta secretion from mononuclear phagocytes by tetracyclines. J. Antimicrob. Chemother. 26 (1990) 61–70.
Kloppenburg, M., Breedveld, F. C., Miltenburg, A. M., Dijkmans, B. A. Antibiotics as disease modifiers in arthritis. Clin. Exp. Rheumatol. 11 (Suppl. 8) (1993) S113-S115.
Ingham, E., Turnbull, L., Kearney, J. N. The effects of minocycline and tetracycline on the mitotic response of human peripheral blood-lymphocytes. J. Antimicrob. Chemother. 27 (1991) 607–617.
Manzella, J. P., Clark, J. K. Effects of quinolones on mitogen-stimulated human mononuclear leucocytes. J. Antimicrob. Chemother. 21 (1988) 183–186.
Konno, S., Adachi, M., Asano, K., Okamoto, K., Takahashi, T. Inhibition of human T-lymphocyte activation by macrolide antibiotic, roxithromycin. Life Sci. 51 (1992) 231–236.
Van den Bogert, C., Melis, T. E., Kroon, A. M. Mitochondrial biogenesis during the activation of lymphocytes by mitogens: the immunosuppressive action of tetracyclines. J. Leukoc. Biol. 46 (1989) 128–133.
Gismondo, M. R., Chisari, G., Lo-Bue, A. M. Effect of ampicillin and sulbactam/ampicillin on the immune system. J. Int. Med. Res. 19 (Suppl. 1) (1991) 24A-28A.
Ehlers, S., Hahn, H. The influence of ciprofloxacin treatmentin vivo on cell-mediated immunity toListeria monocytogenes. Zentralbl. Bakteriol. Mikrobiol. Hyg. A. 268 (1988) 259–270.
Munno, I., Arpinelli, F., Benedetti, M., Spoglianti, R., Ferlini, A. The effect of ofloxacin on the immune system of elderly patients. J. Antimicrob. Chemother. 25 (1990) 455–458.
Scordamaglia, A., Bagnasco, M., Borella, F., Colombo, F., Ciprandi, G., Canonica, G. W. Effects of tetroxoprim and sulfadiazine on T lymphocyte proliferation and gamma-interferon production. J. Chemother. 1 (1989) 207–210.
Valcke, Y., Van der Straeten, M. Changes in lymphocyte subpopulations in patients treated with cefodizime for acute lower respiratory tract infections. Infection 20 (Suppl. 1) (1992) S58-S60.
Mazuran, R., Tomasic, J., Broketa, G., Schrinner, E. Immunophenotypization of cells involved in local immune response and serum antibodies in cephalosporin-treated mice. Drugs. Exp. Clin. Res. 17 (1991) 445–450.
Mallmann, P., Bruhl, P. Immunological effects of cefodizime in patients undergoing antineoplastic chemotherapy. Infection 20 Suppl. 1 (1992) S67-S70.
Mallmann, P., Bruhl, P., Dagrosa, E. E., Reeves, A. Effect of cefodizime on parameters of cell-mediated immunityin vitro. Arzneimittelforschung 42 (1992) 567–570.
Tomazic, J., Kotnik, V., Wraber, B. In vivo administration of azithromycin affects lymphocyte activityin vitro. Antimicrob. Agents Chemother. 37 (1993) 1786–1789.
Barriga-Ibars, C., Muriel, E., Benitez, P., de la Fuente, M. Effects of imipenem and cefmetazol on lymphocyte receptors CD2, Fc and C3b of complement. Comp. Immunol. Microbiol. Infect. Dis. 14 (1991) 297–302.
Petit, J. C., Burghoffer, B., Richard, G., Daguet, G. L. Effect of imipenem (N-formimidoyl-thienamycin) on thein-vitro lymphocyte proliferation. J. Antimicrob. Chemother. 20 (1987) 871–874.
Henry-Toulme, N., Hermier, B., Seman, M. Immunomodulating properties of the N-(1-deoxy-D-fructos-lyl) derivative of amphotericin B in mice. Immunol. Lett. 20 (1989) 63–67.
Konno, S., Adachi, M., Asano, K., Kawazoe, T., Okamoto, K., Takahashi, T. Influences of roxithromycin on cell-mediated immune responses. Life. Sci. 51 (1992) 107–112.
Exon, J. H., Stevens, M. G., Koller, L. D., Mather, G. G. Immunotoxicity assessment of gentamicin and liquamycin. Vet. Hum. Toxicol. 31 (1989) 427–430.
Stokes, D. C., Shenep, J. L., Fishman, M., Hildner, W. K., Bysani, G. K., Rufus, K. Polymyxin B prevents lipopolysaccharide-induced release of tumor necrosis factor-alpha from alveolar macrophages. J. Infect. Dis. 160 (1989) 52–57.
Konno, S., Asana, K., Kurokawa, M., Ikeda, K., Okamoto, K., Adachi, M. Antiasthmatic activity of a macrolide antibiotic, roxithromycin: analysis of possible mechanismsin vitro andin vivo. Int. Arch. Allergy. Immunol. 105 (1994) 308–316.
Raponi, G., Ghezzi, M. C., Mancini, C., Filadoro, F. Preincubation ofCandida albicans strains with amphotericin B reduces tumor necrosis factor alpha and interleukin-6 release by human monocytes. Antimicrob. Agents Chemother. 37 (1993) 1958–1961.
Roche, Y., Fay, M., Gougerot-Pocidalo, M. A. Effects of quinolones on interleukin 1 productionin vitro by human monocytes. Immunopharmacology 13 (1987) 99–109.
Bendtzen, K., Diamant, M., Faber, V. Fusidic acid, an immunosuppressive drug with functions similar to cyclosporin A. Cytokine 2 (1990) 423–429.
Roche, Y., Fay, M., Gougerot-Pocidalo, M. A. Interleukin-1 production by antibiotic-treated human monocytes. J. Antimicrob. Chemother. 21 (1988) 597–607.
Tokuda, Y., Tsuji, M., Yamazaki, M., Kimura, S., Abe, S., Yamaguchi, H. Augmentation of murine tumor necrosis factor production by amphotericin Bin vitro andin vivo. Antimicrob. Agents Chemother. 37 (1993) 2228–2230.
Hirakata, Y., Kaku, M., Mizukane, R., Ishida, K., Furuya, N., Matsumoto, T., Tateda, K., Yamaguchi, K. Potential effects of erythromycin on host defense systems and virulence ofPseudomonas aeruginosa. Antimicrob. Agents Chemother. 36 (1992) 1922–1927.
Kita, E., Sawaki, M., Nishikawa, F., Mikasa, K., Yagyu, Y., Takeuchi, S., Yasui, K., Narita, N., Kashiba, S. Enhanced interleukin production after long-term administration of erythromycin stearate. Pharmacology 41 (1990) 177–183.
Kita, E., Sawaki, M., Mikasa, K., Hamada, K., Takeuchi, S., Maeda, K., Narita, N. Alterations of host response by a long-term treatment of roxithromycin. J. Antimicrob. Chemother. 32 (1993) 285–294.
Chia, J. K., Pollack, M. Amphotericin B induces tumor necrosis factor production by murine macrophages. J. Infect. Dis. 159 (1989) 113–116.
Tufano, M. A., Cipollaro de l'Ero, G., Ianniello, R., Baroni, A., Galdiero, F. Antimicrobial agents induce monocytes to release IL-1 alpha, IL-6, and TNF, and induce lymphocytes to release IL-4 and TNF tau. Immunopharmacol. Immunotoxicol. 14 (1992) 769–782.
Petit, J. C., Daguet, G. L., Richard, G., Burghoffer, B. Influence of ciprofloxacin and piperacillin on interleukin-1 production by murine macrophages. [Letter] J. Antimicrob. Chemother. 20 (1987) 615–617.
Bailly, S., Pocidalo, J. J., Fay, M., Gougerot-Pocidalo, M. A. Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin. Antimicrob. Agents Chemother. 35 (1991) 2016–2019.
Damais, C., Jupin, C., Parant, M., Chedid, L. Induction of human interleukin-1 production by polymyxin B. J. Immunol. Methods 101 (1987) 51–56.
Neal, D. E., Kaack, M. B., Baskin, G., Roberts, J. A. Attenuation of antibody response to acute pyelonephritis by treatment with antibiotics. Antimicrob. Agents Chemother. 35 (1991) 2340–2344.
Villa, M. L., Valenti, F., Scaglione, F., Falchi, M., Fraschini, F. In-vivo andin-vitro interference of antibiotics with antigen-specific anti-body responses: effect of josamycin. J. Antimicrob. Chemother. 24 (1989) 765–774.
Akahane, K., Furuhama, K., Kato, M., Une, T., Onodera, T. Influences of cephem antibiotics on the immune response in mice. Chemotherapy 36 (1990) 300–307.
Corrales, I., Suarez, A., Lima, A., Ballestero, S., Gomez-Lus, M. L., Prieto, J. Clindamycin and tetracycline as immunomodulating agents: anin vivo study. Drugs. Exp. Clin. Res. 15 (1989) 409–415.
Villa, M. L., Valenti, F., Mantovani, M., Scaglione, F., Clerici, E. Macrolidic antibiotics: effects on primaryin vitro antibody responses. Int. J. Immunopharmacol. 10 (1988) 919–924.
Ventura, M. M., Romagnoli, M., Santucci, S., Sforza, C., Gatti, G., Carandente, O. Cefodizime administration in healthy subjects: studies of natural killer cells, urinary hormones and electrolytes. Chronobiologia 15 (1988) 43–59.
Agostoni, C., Giovannini, M., Fraschini, F., Scaglione, F., Galluzzo, C., Riva, E., Ferrara, F. Comparison of miocamycin versus amoxycillin in lower respiratory tract infections in children. Clinical response and effect on natural killer activity. J. Int. Med. Res. 16 (1988) 305–311.
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Van Vlem, B., Vanholder, R., De Paepe, P. et al. Immunomodulating effects of antibiotics: Literature review. Infection 24, 275–291 (1996). https://doi.org/10.1007/BF01743360
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DOI: https://doi.org/10.1007/BF01743360