Circulating Interleukin-1 and Tumor Necrosis Factor in Septic Shock and Experimental Endotoxin Fever

Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes.