Effect of interleukin-10 (IL-10) on experimental LPS-induced acute lung injury.
The purpose of this study was to clarify the role of interleukin-10 (IL-10) during the development of acute lung injury induced by lipopolysaccharide (LPS) in a mouse model. When LPS was given to nude mice, the mortality rate was 100% at 48 h of the observation period. However, mortality was reduced to 30% when IL-10 was added concomitantly (P < 0.01). In the IL-10 group, a significant reduction of inflammatory change in lung tissue was observed. It was also found that peripheral neutrophils increased when IL-10 was added. When LPS and IL-10 were given concomitantly, the level of tumor necrosis factor (TNF)-alpha in both serum and bronchoalveolar lavage fluid (BALF) decreased significantly (P < 0.05). In-vitro observations were made concerning the influence of human neutrophils. Both neutrophil superoxide (O2-) and elastase production were increased by TNF-alpha stimulation, while significant inhibition was seen with the concomitant dosing of IL-10 (P < 0.05). TNF-alpha stimulation increased the occurrence of adhesion molecules for neutrophil surface, lymphocyte function-associated antigen-1 (LFA-1), and macrophage antigen-1 (Mac-1). LPS stimulation greatly increased the occurrence of neutrophil surface 55-kDa TNF-receptor [TNF-R (p55)], when observation was made under laser microscopy. However, no significant occurrence was seen with IL-10 concomitant dosing. The above results suggested that IL-10 inhibited TNF-alpha production and neutrophil activity in LPS-induced acute lung injury, which led to a reduction of the lung tissue injury.
Inoue
G
G
First Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. kakaka@dl.dion.ne.jp
D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D016753:Interleukin-10