Blocking IL-1 and TNF

There is little question that the major advance in treating patients with s eptic shock was the availability of broad spectrum antibiotics. The field e ntered a new era when it was shown that neutralizing antibodies to the infl ammatory cytokine tumor necrosis factor (TNF) prevented death in mice, rabb its, or baboons, given a lethal injection of Escherichia coli or endotoxin. Similar results were observed with high doses of IL-1 in animals. Injectin g a combination of low doses of IL-1 plus TNF revealed that these two cytok ines acted synergistically in inducing a shock-like state. For the patient without overt infection, for example multiple trauma, the preclinical data demonstrated that the systemic injection of either IL-1 or TNF into experim ental animals induced physiological, hematological and pathological changes which were nearly identical to those observed during bacteremia or multipl e trauma. Therefore, there was no lack of data that supported the concept t hat blocking IL-1 and/or TNF would reduce mortality in patients with septic shock or systemic inflammation. Although the clinical trials in septic pat ients have not resulted in any approved anti-IL-1 or anti-TNF products, the concept continues to have brand support based on the biology of these cyto kines.