PMID: 9444610Jan 28, 1998Paper

Combination immunotherapy which neutralises the effects of TNF alpha and IL-1 beta attenuates the circulatory failure and multiple organ dysfunction caused by endotoxin in the rat

Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society
H Ruetten, Christoph Thiemermann

Abstract

Pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF alpha) or interleukin-1 beta (IL-1 beta) are implicated in the pathogenesis of septic shock. Here we investigate the role of endogenous TNF alpha and IL-1 beta on (i) the circulatory failure, (ii) the multiple organ dysfunction syndrome (MODS) and (iii) the induction of the inducible isoform of nitric oxide (NO) synthase (iNOS) caused by endotoxin (LPS) in the anaesthetised rat. Here we demonstrate that (i) a polyclonal antibody against TNF alpha, (ii) a polyclonal antibody against IL-1, (iii) co-administration of polyclonal antibodies against TNF alpha and IL-1 and (iv) neutralisation of the effects of both TNF alpha and IL-1 with one polyclonal antibody directed against both cytokines reduces the circulatory failure, the liver injury/dysfunction, the pancreatic injury (but not the renal dysfunction) caused by endotoxin in the rat. The beneficial effects of these interventions on haemodynamics and organ injury/dysfunction are most likely due to prevention of the induction of iNOS. The two different interventions which neutralised the effects of both TNF alpha and IL-1 were superior in reducing the circulatory failure and the organ injury caused by endotoxin i...Continue Reading

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