Tumour necrosis factor production in fulminant hepatic failure: relation to aetiology and superimposed microbial infection

Author:

DE LA MATA M1,MEAGER A2,ROLANDO N1,DANIELS H M1,NOURI-ARIA K T1,GOKA A K J1,EDDLESTON A L W F1,ALEXANDER G J M1,WILLIAMS R1

Affiliation:

1. The Liver Unit, Kings College School of Medicine & Dentistry, London, England

2. National Institute for Biological Standards and Control, South Mimms, Potters Bar, England

Abstract

Summary Tumour necrosis factor-alpha (TNF-α), a cytokine derived from macrophages, is considered to bean important endogenous mediator of endotoxic shock. Patients with fulminant hepatic failure are particularly susceptible to infection and the development of multi-organ failure and similarities to endotoxic shock suggest a possible pathogenetic role for TNF in fulminant hepatic failure. In vitro TNF production was therefore investigated serially in 21 consecutive patients with fulminant hepatic failure and in 21 healthy controls. Spontaneous and lipopolysaccharide-stimulated TNF production were elevated in viral-induced fulminant hepatic failure, compared with healthy controls (P < 0.05 and P <0.01, respectively). By contrast, patients with paracetamol-induced fulminant hepatic failure had normal spontaneous and lipopolysaccharide-stimulated TNF production, while those who died had significantly reduced spontaneous TNF production compared with survivors (P < 0.02); this difference was present throughout admission. In this group elevations in TNF production above baseline were associated with Gram-positive bacterial or fungal infection but not Gram-negative bacterial infection. There was no correlation between any of the clinical complications of fulminant hepatic failure and TNF production. These studies indicate that TNF is produced in response to microbial stimuli in fulminant hepatic failure, but do not support a direct role for TNF in the evolution of the clinical complications of fulminant hepatic failure.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

Reference30 articles.

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