Clin. exp. Immunol. (1990) 82, 479-484
Tumour necrosis factor production in fulminant hepatic failure: relation to aetiology and superimposed microbial infection M. DE LA MATA, A. MEAGER,* N. ROLANDO, H. M. DANIELS, K. T. NOURI-ARIA, A. K. J. GOKA, A. L. W. F. EDDLESTON, G. J. M. ALEXANDER & R. WILLIAMS The Liver Unit, King's College School of Medicine & Dentistry, London, and *National Institute for Biological Standards and Control, South Mimms, Potters Bar, England
(Accepted for publication 29 June 1990)
SUMMARY Tumour necrosis factor-alpha (TNF-a), a cytokine derived from macrophages, is considered to be an 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 1000 u/ml after LPS stimulation (P < 0-01) (Table 1). Corresponding values on admission were
Table 1. Peak tumour necrosis factor (TNF) production (U/ml) in fulminant failure (FHF)
hepatic
With
LPS
Without
LPS
Range
Groups
n
Median
Range
Median
Control Patients Viral FHF Paracetamol-induced FHF
21 21 6 14
265 420 > 1000 345
41-800* 5->1000 320- 1000* 4-> 1000
6
1000 4-560
Survivors (n = 5) Admission Peak Final
460 460 420
43- > 1000 43- >1 000 16- >1000
LPS, lipopolysaccharide. *P 000 U/ml.
Paracetamol-induced FHF A wide range of values was observed in this group (Table Fig. 1). TNF production was not significantly different from the control group at any stage. However, when survival was considered, a significant association between low TNF production and fatal outcome became apparent. Nine of the 14 patients died and five survived. Both spontaneous and LPS-stimulated production were consistently lower in those who died, whether
482
M. de la Mata et al. Table 3. Lipopolysaccharide-stimulated tumour necrosis factor (TNF) production and superimposed microbial infection in fulminant hepatic failure Patient no.
Aetiology
Organism
Source
TNF (U/ml)
POD
Staphylococcus aureus Candida albicans S. aureus S. aureus Klebsiella pneumoniae S. aureus Escherichia coli E. coli K. pneumoniae
Blood Blood Sputum Blood Urine Sputum Urine Blood Blood
> 1000 > 1000 > 1000 < 1000 > 1000 > 1000 > 1000 150 4
1 I 2 3 3 4 4
AFLP POD
5 6
POD POD
Viral
Values given for TNF production are those temporally related to the positive cultures. POD, paracetamol overdose; AFLP, acute fatty liver of pregnancy.
150r r.. P