Role of endogenous cytokines in endotoxin- 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 O2 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 O2 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 O2 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 O2 tolerance. In contrast, IL-1ra completely abolished IL-1-induced inflammatory response and markedly inhibited IL-1-induced O2 tolerance. These results suggest that LPS-induced alveolar inflammatory response and O2 tolerance are not mediated by endogenous TNF and IL-1. Similarly, endogenous TNF does not mediate IL-1-induced alveolar inflammatory response and O2 tolerance.
Tang
G
G
Research Service, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, NY 12208.
White
J E
JE
Lumb
P D
PD
Lawrence
D A
DA
Tsan
M F
MF
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D007158:Immunologic Techniques; D007249:Inflammation / Q000139:chemically induced; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010100:Oxygen / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D004731:Endotoxins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen