Intratracheal administration of endotoxin and cytokines. IV. The soluble tumor necrosis factor receptor type I inhibits acute inflammation.

Endotoxin lipopolysaccharide (LPS) administered intratracheally to rats causes pulmonary tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) production and results in acute broncho-alveolar neutrophilic inflammation. In the present study, the recombinant human TNF soluble receptor type I (sTNFrI) co-injected intratracheally with LPS is shown to inhibit significantly (P < 0.0001) the number of neutrophils in bronchoalveolar lavage specimens at 6 hours as compared to intratracheal injection of LPS alone. The sTNFrI was at least as effective as the recombinant human IL-1 receptor antagonist (IL-1ra) as an inhibitor of acute inflammation. Inhibition of LPS-induced acute inflammation by the combination of sTNFrI and IL-1ra was not significantly more than the inhibition afforded by sTNFrI alone. Intratracheal co-injection of sTNFrI with LPS unexpectedly increased TNF levels in BAL specimens, perhaps by changing the normal catabolism of TNF. On the other hand, co-injection of sTNFrI and LPS decreased IL-6 levels in BAL fluid, most likely by interfering with the induction of IL-6 by TNF. The sTNFrI may prove to be an important pharmacological down-regulator of acute inflammation.