EXPERIMENTAL THERAPIES FOR SEPSIS DIRECTED AGAINST TUMOR-NECROSIS-FACTOR

Tumour necrosis factor (TNF) has been identified as an important media tor involved in the generation of sepsis syndrome. Two major strategie s have evolved for counteracting the effects of TNF in patients with s evere manifestations of sepsis: neutralization by anti-TNF antibodies and competitive antagonism of TNF with synthetic soluble TNF receptors . Clinical trials with murine monoclonal antibodies against TNF have s hown that this agent is able to reduce early morbidity and mortality, but with no reduction in 28 day mortality. A clinical study with a syn thetic 75 kDa soluble TNF receptor failed to show any benefit with thi s drug and indeed there was higher mortality at higher doses. Trials o f a 55 kDa soluble TNF receptor are continuing and this drug is appare ntly safe. Drugs that modify TNF in vivo may be a useful component of future management of sepsis, either as monotherapy or as part of a com bined strategy of immunomodulation.