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

TLDR

Plasma IL‑1β, IL‑1α, and TNF‑α were quantified by radioimmunoassay in 44 healthy controls, 15 septic shock patients, and 6 endotoxin‑infused volunteers. Septic patients exhibited markedly higher plasma IL‑1β and TNF‑α levels, with IL‑1β modestly elevated after endotoxin infusion while TNF‑α rose 15‑fold more rapidly and correlated with illness severity, and IL‑1β and TNF‑α concentrations were independently regulated and associated with distinct clinical outcomes.

Abstract

Interleukins (IL)-1β and -1α and tumor necrosis factor (TNF-α) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1α levels were low (40 pg/ml) or undetectable in all situations. In 67% ofthe healthy subjects, plasma IL-1β levels were <70 pg/ml. Septic patients had higher plasma IL-1β levels (120± 17pg/ml, P =.001);those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-α 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-1β and TNF-α concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1β, from a baseline of 35 ± 5 pg/ml to a maximum of 69 ± 27 pg/ml at 180min (P <.05). Peak TNF-a levels after endotoxin infusion were 15 times higher than IL-1β levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1β levels. These data support the concept that plasma IL-1β and TNF-α concentrations are regulated independently and are associated with different clinical outcomes.