Abstract
Increased plasma tumour necrosis factor α (TNF) concentration correlates with mortality in sepsis. We suggested that pentoxifylline (PTXF), which is known to inhibit TNF production, may improve survival and attenuate clinical symptoms of sepsis in neonates. Plasma TNF levels were evaluated in 29 newborn infants with sepsis. Patients were randomly assigned into two groups, receiving PTXF in a dose of 5 mg/kg per hour for 6 h or placebo (saline), on 3 successive days. Both groups were subjected to the same conventional therapy. TNF was evaluated before and after PTXF or placebo administration on the 1 st and 3rd days of therapy. There was a statistically significant decrease in plasma TNF level in the PTXF group when the values before the first and after the last PTXF infusion were compared [mean: 671.5 pg/ml; SD: 438; med: 729.6 vs mean: 41.0 pg/ml; SD: 64.1; med: 11.5;P<0.000004]. In the placebo group, decrease was not significant [mean: 633.0 pg/ml SD: 488.6; med: 618.9 vs 246.9 pg/ml; SD: 243.9; med: 191.0]. A significantly higher plasma TNF level, evaluated after the last PTXF infusion, was found in the placebo group [246,9 pg/ml vs 41.0 pg/ml;P<0.001]. Only one of four infants with signs of shock in the placebo group survived, whereas all of five newborns with symptoms of shock in the PTXF group survived [P<0.04]. An increased incidence of metabolic acidosis [P<0.05], necrotizing enterocolitis [P<0.04] and renal insufficiency [P<0.05] was observed in infants in the placebo group.
Conclusion
PTXF inhibits production of TNF and may have therapeutic value in the treatment of premature infants with sepsis complicatea by shock.
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Abbreviations
- FiO 2 :
-
fraction of inspired oxygen
- NEC :
-
necrotizing enterocolitis
- PTXF :
-
pentoxifylline
- TNF :
-
tumour necrosis factor-alpha
References
Bell M, Ternberg J, Feigin R (1978) Neonatal necrotizing enterocolitis. Therapeutic decision based upon clinical staging. Ann Surg 187:1–7
Beutler B, Cerami A (1987) Cachectin: more than a tumor necrosis factor. N Engl J Med 316:379–385
Debets JM, Kampmeijer R, Linden MP van der, Meer JW van der (1989) Plasma tumor necrosis factor in septic shock and mortality in critically ill septic patients. Crit Care Med 17: 489–494
Girardin EP, Berner ME, Grau GE, Suter S, Lacourt G, Paunier L (1990) Serum tumour necrosis factor in newborns at risk for infections. Eur J Pediatr 149:645–647
Harris MC, Costarino AT, Sullivan JS, Dulkerian S, McCawley L, Corcoran L, Butler S, Kilpatrick L (1994) Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis. J Pediatr 124:105–111
Hewett JA, Jean PA, Kunkel SI, Roth RA (1993) Relationship between tumor necrosis factor-alpha and neutrophils in endotoxin-induced liver injury. Am J Physiol 265:G1011–1015
Lauterbach R, Pawlik D, Tomaszczyk B, Cholewa B (1994) Pentoxifylline treatment of sepsis of premature infants. Preliminary clinical observations. Eur J Pediatr 153:672–674
Masouye P, Gunning K, Pittet JF, Suter PM, Morel DR (1992) Xanthine derivative HWA 138 attenuates hemodynamic and oxygen uptake dysfunction secondary to severe endotoxin shock in sheep. Circ Shock 36: 113–119
Mollitt DL, Poulos ND (1991) The role of pentoxifylline in endotoxin-induced alterations of red cell deformability and whole blood viscosity in the neonate. J Pediatr Surg 26:572–574
Rice GC, Brown PA, Nelson RJ, Bianco JA, Singer JW, Bursten S (1994) Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid. Proc Natl Acad Sci USA 91:3857–3861
Samlaska CP, Winfield EA (1994) Pentoxifylline. J Am Acad Dermatol 30:603–621
Steeb GD, Wilson MA, Garrison RN (1992) Pentoxifylline preserves small-intestine microvascular blood flow during bacteriemia. Surgery 112:756–764
Stevens D, Bryant AE, Hackett SP (1993) Sepsis syndromes and toxic shock syndromes: concepts in pathogenesis and a perspective of future treatment strategies. Curr Op Infect Dis 6:373–383
Sullivan JS, Kilpatrick L, Costarino AT, Lee SC, Harris MC (1992) Correlation of plasma cytokine elevations with mortality rate in children with sepsis. J Pediatr 120:510–515
Sun XM, Hsueh W (1988) Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor. J Clin Invest 81: 1328–1332
Van Leenen D, Poll T van der, Levi M, Ten-Cate H, Deventer SJ van, Hack CE, Aarden LA, Ten-Cate JW (1993) Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees. J Immunol 151: 2318–2325
Wang P, Ba ZF, Morrison MH, Ayala A, Chaudry IH (1992) Mechanism of the beneficial effects of pentoxifylline on hepatocellular function after trauma hemorrhage and resuscitation. Surgery 112:451–458
Wang P, Zheng F, Zhou M, Tait MS, Chaudry IH (1993) Pentoxifylline restores cardiac output and tissue perfusion after trauma-hemorrhage and decreases susceptibility to sepsis. Surgery 114:352–359
Zabel P, Wolter DT, Schade UF, Schonharting MM (1989) Oxpentifylline in endotoxemia. Lancet 23: 1474–1477
Zabel P, Leimenstoll G, Schroder P, Elfeldt R, Schlaak M, Niedermayer W (1991) Pentoxifylline suppresses OKT3-induced tumor necrosis factor alpha formation in renal transplant recipients. Z Tr Med 3:62–65
Zembala M, Siedlar M, Ruggiero I, Wieckiewicz J, Mytar B, Mattei M, Colizzi V (1994) The MHC class II and CD 44 molecules are involved in the induction of tumour necrosis factor (TNF) gene expression by human monocytes stimulated with tumour cells. Int J Cancer 56:269–274
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Lauterbach, R., Zembala, M. Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis. Eur J Pediatr 155, 404–409 (1996). https://doi.org/10.1007/BF01955273
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DOI: https://doi.org/10.1007/BF01955273