Abstract
The role of the human immunodeficiency virus type-1 (HIV) in producing intestinal disease was studied prospectively in 74 HIV-infected individuals with (43) or without (31) the acquired immunodeficiency syndrome (AIDS). Thirty-one subjects had enteric infections; all but one had AIDS. Alteration in bowell habits was the most common symptom and occurred independently of enteric infections. Abnormal histopathology was present in 69% of cases, and the finding was associated with altered bowel habits. An HIV-associated protein, p24, was detected in 71% of biopsies by ELISA assay. Tissue p24 contents varied with disease stage and were highest in HIV-infected individuals without AIDS (Walter Reed classes 3 and 4). Tissue p24 detection was associated with both altered bowel habits and histologic mucosal abnormalities. Tissue contents of the cytokines, tumor necrosis factor-α and interleukin-1β, were higher in HIV-infected individuals than in controls and their elevations were independent of enteric infection. We conclude that HIV reactivation in the intestinal mucosa may be associated with an inflammatory bowel syndrome in the absence of other enteric pathogens.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Kotler DP: Intestinal and hepatic manifestations of AIDS. Adv Intern Med 34:43–71, 1988
Quinn TC: Gastrointestinal manifestations of human immunodeficiency virus.In Current Topics in AIDS, vol 1. MS Gottlieb (ed). New York, John Wiley & Sons, 1987, p 155
Sewankambo N, Mugerwa RD, Goodgame R, et al: Enteropathic AIDS in Uganda. An endoscopic, histological, and microbiological study. AIDS 1:9–16, 1987
Smith PD, Lane HC, Gill VJ, et al: Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 108:328–333, 1988
Dworkin B, Wormser GP, Rosenthal WS, et al: Gastrointestinal manifestations of the acquired immunodeficiency syndrome: A review of 22 cases. Am J Gastroenterol 80:774–779, 1985
Antony MA, Brandt LJ, Klein RS, Bernstein LH: Infectious diarrhea in patients with AIDS. Dig Dis Sci 33:1141–1146, 1988
Colebunders R, Lusakumuni K, Nelson AM, et al: Persistent diarrhea in Zairian AIDS patients: An endoscopic and histologic study. Gut 29:1697–1691, 1988
Dobbins WO, Weinstein WM: Electron microscopy of the intestine and rectum in acquired immunodeficiency syndrome. Gastroenterology 88:738–749, 1985
Kotler DP, Gaetz HP, Klein EB, Lange M, Holt PR: Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med 101:421–428, 1984
Gillin JS, Shike M, Alcock N, et al: Malabsorption and mucosal abnormalities of the small intestine in the acquired immunodeficiency syndrome. Ann Intern Med 102:619–624, 1985
Ullrich R, Zeitz M, Heise M, L'age M, Hoffken G, Rieken EO: Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): Evidence for HIV-induced enteropathy. Ann Intern Med 111:15–21, 1989
Kotler DP, Reka S, Borcich A, Cronin WJ: Detection, localization and quantitation of HIV-associated antigens in intestinal biopsies from HIV-infected patients. Am J Pathol 139:823–830, 1991
Fox CH, Kotler DP, Tierney AR, Wilson CS, Fauci AS: Detection of HIV-1 RNA in intestinal lamina propria of patients with AIDS and gastrointestinal disease. J Infect Dis 159:467–471, 1989
Nelson JA, Wiley CA, Reynolds-Kohler C, et al: Human immunodeficiency virus detected in bowel epithelium from patients with gastrointestinal symptoms. Lancet 2:259–262, 1988
Rene E, Jarry A, Brousse N, et al: Demonstration of HIV infection of the gut in AIDS patients: Relation with symptoms and other digestive infection. Gastroenterology 94:373A, 1988 (abstract)
Narayan O, Clements JE: Biology and pathogenesis of lentiviruses. J Gen Virol 70:1617–1639, 1989
Hoover EA, Mullin JI, Quackenbush SL, Gasper PW: Experimental transmission and pathogenesis of immunodeficiency syndrome in cats. Blood 70:1880–1892, 1987
Centers for Disease Control: Classification system for human T-lymphotropic virus type III/Lymphadenopathy-associated virus infections. Ann Intern Med 105:2343–2347, 1986
Clayton F, Cronin WJ, Reka S, Torlakovic E, Sigal S, Kotler DP: Rectal mucosal histopathology in HIV infection varies with disease stage and HIV protein content. Gastroenterology 103:919–933, 1992
Redfield RR, Wright DC, Tramont EC: The Walter Reed staging classification for HTL VIII/LAV infection (special report). N Engl J Med 314:23–27, 1986
Sharon P, Ligumsky M, Rachmilewitz D: Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalasine. Gastroenterology. 75:638–640, 1978
Ligumsky M, Karmeli F, Sharon P, Zor U, Cohen F, Rachmilewitz D: Enhanced thromboxane A2 and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroids and sulfasalasine. Gastroenterology 81:444–449, 1981
Sharon P, Stenson WF: Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology 86:453–460, 1984
Blair IA, Brash AR, Daugherty J, FitzGerald GA: Quantitative analysis of leukotriene B4 in human serum. Adv in Prostaglandin, Thromboxane, Leukotriene Res 15:61–65, 1985
Kaljot KT, Ling JP, Gold JWM: Prevalence of acute enteric viral pathogens in acquired immunodeficiency syndrome patients with diarrhea. Gastroenterology 97:1031–1032, 1989
Laughon BE, Druckman DA, Vernon A, et al: Prevalence of enteric pathogens in homosexual men with and without acquired immunodeficiency syndrome. Gastroenterology 94:984–989, 1988
Cooper C, Cotton DWK, Hudson MJ, Kirkham N, Wilmott FEW: Rectal spirochaetosis in homosexual men: characterization of the organisms and pathophysiology. Genitourin Med 62:47–52, 1986
Adachi A, Koenig S, Gendelman HE, et al: Productive, persistent infection of human colorectal cell lines with human immunodeficiency virus. J Virol 61:209, 1987
Moyer MP, Ramirez A Jr, McKee-Suarez MS, Gendelman HE: Human immunodeficiency virus (HIV) infection of gastrointestinal (GI) cell cultures. VI International Conference on AIDS. 2:140, 1990
Evans L, Corbell JE, Edwards P, Vasak E, Cooper D, Penny R: Infection of colon epithelial cells by HIV-1. VI International Conference on AIDS. 2:141, 1990
Smith PD: Role of cytokines in infectious and noninfectious enteropathy in patients with AIDS. Immunol Res 10:447–451, 1991
Ehrenpreis ED, Patterson RK, Brainer JA: Histopathologic findings of duodenal biopsy specimens in HIV-infected patients with and without diarrhea and malabsorption. Am J Clin Pathol 97:21–28, 1992
Aziz DC, Hanna A, Jolicoeur P: Severe immunodeficiency disease induced by a defective murine leukemia virus. Nature 338:505–508, 1989
Walker BD, chakrabarti S, Moss B, et al: HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 328:345–348, 1987
Rook AH, Lane HC, Folks T, et al: Sera from HTL VIII/LAV antibody positive individuals mediate antibody dependent cellular cytotoxicity against HTL VIII/LAV infected T cells. J Immunol 138:1064–1067, 1987
Tyler DS, Nastala CL, David Stanley S, et al: GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals; evidence for circulating CD16+ effector cells armedin vivo with cytophilic antibody. J Immunol 142:1177–1182, 1989
Koup RA, Sullivan JL, Levine PH, et al: Antigen specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera. J Virol 63:584–590, 1989
Weiss L, Haelffner-Cavaillon N, Laude M, Gilquin J, Kazatchkine MD: HIV infection is associated with the spontaneous production of interleukin-1 (IL-1)in vivo and with an abnormal release of IL-1 alphain vitro. AIDS 3:695–699, 1989
Nakajima K, Martinez-Maza O, Hirano T, et al: Induction of IL-6 (B cell stimulatory factor-2/IFNb2) production by HIV. J Immunol 142:531–537, 1989
Chang EB, Musch MW, Mayer L: Interleukins 1 and 3 stimulate anion secretion in chicken intestine. Gastroenterology 98:1518–1524, 1990
Rosenberg ZF, Fauci AS: Minireview: Induction of expression of HIV in latently or chronically infected cells. AIDS Res Hum Retrovir 5:1–4, 1989
Folks T, Justement J, Kinter A, Dinarello C, Fauci AS: Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 238:800–802, 1987
Koyanagi Y, O'Brien WA, Zhao JQ, Golde DW, Gasson JC, Chen ISY: Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Science 241:1673–1675, 1988
Folks TM, Clouse KA, Justement, et al: Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci USA 86:2365–2368, 1989
Duh EJ, Maury WJ, Folks TM, Fauci AS, Rabson AB: Tumor necrosis factor A activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF kappa B sites in the long terminal repeat. Proc Natl Acad Sci USA 86:5874–5878, 1989
Kuno S, Ueno R, Hayaishi O, Nakashima H, Harada S, Yakamoto N: Prostaglandin E2, a seminal constituent, facilitates the replication of acquired immune deficiency syndrome virus in vitro. Proc Natl Acad Sci USA 83:3487–3490, 1986
Kotler DP, Reka S: Modulation of HIV production by rectal mucosain vitro. Gastroenterology 98:457A, 1990 (abstract)
Michalek SM, Moore RN, McGhee JR, Rosenstreich DI, Mergenhagen SE: The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxin. J Infect Dis 141:155–163, 1980
Kapembwa MS, Fleming SC, Sewankambo N, Serwadda D, Griffin GE: Altered small-intestinal permiability associated with diarrhea in human immunodeficiency virus infected caucasians and african subjects. Clin Sci 81:327–334, 1991
Jalkanen S, Streeter P, Lakey E, Bargatze R, Butcher EC: Lymphocyte and endothelial cell recognition elements that control lymphocyte traffic to mucosa-associated lymphatic tissues. Monogr Allergy 24:144–149, 1988
Streiter RM, Kunkel SL, Showell HJ, et al: Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science 243:1467–1468, 1989
Folks TM, Kelly J, Benn S, et al: Susceptibility of normal human lymphocytes to infection by HTLV-III/LAV. J Immunol 136:4049–4053, 1986
Kotler DP, Reka S, Hecker L, Cohen S, Clayton F, Tierney AR: Treatment of HIV-associated mucosal inflammation with oral 5-ASA. Gastroenterology 102:648A, 1992
Author information
Authors and Affiliations
Additional information
This work was supported in part by Grant 21414 from the National Institutes of Health.
Rights and permissions
About this article
Cite this article
Kotler, D.P., Reka, S. & Clayton, F. Intestinal mucosal inflammation associated with human immunodeficiency virus infection. Digest Dis Sci 38, 1119–1127 (1993). https://doi.org/10.1007/BF01295730
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01295730