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 against O-2 toxicity. However, whether the effect of endotoxin is mediated by these cytokines is not clear. We have previously demonstrated that depletion of 84% rat alveolar macrophages (AM), which reduced lipopolysaccharide (LPS)-induced release of TNF by 86%, had no effect on LPS-induced O-2 tolerance. In this study, we demonstrated that coinsufflation of LPS with anti-TNF antibody and IL-1 receptor antagonist (IL-1ra), which completely inhibited LPS-induced TNF and IL-1 activities, had no effect on LPS-induced alveolar inflammatory response and O-2 tolerance. Likewise, coinsufflation of IL-1 and anti-TNF antibody, which completely neutralized IL-1-induced TNF activity, had no effect on IL-1-induced alveolar inflammatory response and O-2 tolerance. In contrast, IL-1ra completely abolished IL-1-induced inflammatory response and markedly inhibited IL-1-induced O-2 tolerance. These results suggest that LPS-induced alveolar inflammatory response and O-2 tolerance are not mediated by endogenous TNF and IL-1. Similarly, endogenous TNF does not mediate IL-1-induced alveolar inflammatory response and O-2 tolerance.