REGULATORY EFFECTS OF INTERLEUKIN-10 ON LUNG ISCHEMIA-REPERFUSION INJURY

Objective: Interleukin-10, a cytokine with antiinflammatory activities , was studied to determine its effects on development of early lung re perfusion injury, Methods: Adult male rats underwent 90 minutes of lef t lung ischemia followed by 4 hours of reperfusion, Time-matched sham- operated control rats underwent hilar dissection but not lung ischemia , Lung injury was measured by vascular permeability to bovine serum al bumin tagged with iodine 125, To evaluate the effect of exogenous inte rleukin-10, additional animals received interleukin-10 intravenously b efore ischemia, To assess the role of endogenous interleukin-10, anima ls received rabbit antimouse interleukin-10 immunoglobin G (or preimmu ne rabbit immunoglobin G) before ischemia, Results: Compared with sham control rats, ischemia-reperfusion control rats demonstrated signific antly more lung injury, Animals receiving interleukin-10 had significa ntly less lung injury than did ischemia-reperfusion control rats, Anim als receiving antiinterleukin-10 had significantly more lung injury th an did animals receiving preimmune immunoglobin G, Alveolar macrophage s from animals after 90 minutes of lung ischemia produced more tumor n ecrosis factor-alpha in culture than did unstimulated macrophages; thi s production was reduced significantly by the addition of interleukin- 10 to the culture medium, Conclusion: Endogenous interleukin-10 has a protective effect against early lung reperfusion injury, and interleuk in-10 administration can reduce lung reperfusion injury, perhaps in pa rt through its ability to reduce production by alveolar macrophages of tumor necrosis factor-alpha, a known proinflammatory cytokine.