ROLE OF ENDOGENOUS CYTOKINES IN ENDOTOXIN-INDUCED AND INTERLEUKIN-1-INDUCED PULMONARY INFLAMMATORY RESPONSE AND OXYGEN TOLERANCE

Endotoxin lipopolysaccharide and the cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), are known to protect adult rats agains t O-2 toxicity. However, whether the effect of endotoxin is mediated b y these cytokines is not clear. We have previously demonstrated that d epletion of 84% rat alveolar macrophages (AM), which reduced lipopolys accharide (LPS)-induced release of TNF by 86%, had no effect on LPS-in duced O-2 tolerance. In this study, we demonstrated that coinsufflatio n of LPS with anti-TNF antibody and IL-1 receptor antagonist (IL-1ra), which completely inhibited LPS-induced TNF and IL-1 activities, had n o effect on LPS-induced alveolar inflammatory response and O-2 toleran ce. Likewise, coinsufflation of IL-1 and anti-TNF antibody, which comp letely neutralized IL-1-induced TNF activity, had no effect on IL-1-in duced alveolar inflammatory response and O-2 tolerance. In contrast, I L-1ra completely abolished IL-1-induced inflammatory response and mark edly inhibited IL-1-induced O-2 tolerance. These results suggest that LPS-induced alveolar inflammatory response and O-2 tolerance are not m ediated by endogenous TNF and IL-1. Similarly, endogenous TNF does not mediate IL-1-induced alveolar inflammatory response and O-2 tolerance .