Study On Endotoxin-Induced TNF-α,IL-6 Secretion And CD14 Expression On Alveolar Macrophages In Experimental Type 2 Diabetic Rat

Objective:To investigate the mechanism for weakened pulmonary local immune defensive function at levels of cell receptor and immunomolecule in type 2 diabetes mellitus rats with acute lung injury induced by lipopolysaccharide(LPS). Methods: Forty six male Wistar rats were randomly divided into the diabetes group (n=28) and normal control group (n=18). Rats in diabetes group were fed with the diets enriched with high-sucrose and high-lipid. type 2 diabetes mellitus model was developed by intra- peritoneal injection in rats in diabetes group with 35mg/kg of body weight streptozotocin(STZ)in 0.1M citrate buffer (PH=4.2) after 1 month on the diets. Rats in normal control group were fed with regular diets, and received an equal volume of citrate buffer without STZ. Survived rats were divided into four subgroups 4 weeks after STZ injection, including normal control group( Group NC ,7 rats), normal control LPS challenge group( Group NC+LPS ,9 rats) , type 2 diabetes mellitus group( Group DM,11 rats) and type 2 and diabetes mellitus LPS challenge group( Group DM+LPS ,14 rats) . Murine model of endotoxemia/ acute lung injury was produced by injection LPS (1mg/kg of body weight) in isotonic sodium chloride solution via tail vein in Group NC+LPS and Group DM+LPS; Group DM and Group NC rats were injected an equal volume of isotonic sodium chloride solution without LPS. The expression of CD14 on alveolar macrophages (AMs) surface was assayed by immunohistochemistry and then analyzed with computer imaging system. radioimmunological assay were used to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and pulmonary homogenates in various groups .Results: The expression of CD14 on AMs surface and the levels of IL-6,TNF-α in serum in diabetic rats without LPS challenge were significantly higher than those of normal control rats without LPS challenge. There were markedly increased in optical density (OD) values of CD14 and the levels of TNF-α and IL-6 in serum and pulmonary homogenates in both normal control rats and diabetic rats after LPS challenge, but the expression of CD14 on AMs the levels of TNF-α and IL-6 in serum and pulmonary homogenates in diabetic rats after LPS challenge significantly lower than those of normal control rats after LPS challenge. Conclusions: The expression of CD14 on AMs surface and the secretion of TNF-α and IL-6 after LPS challenge are severely decreased in diabetic rats when compared with that of normal controls. This might be one of important mechanisms of weakened pulmonary local immune defensive function in type 2 diabetes mellitus, which is susceptible to pulmonary infection in type 2 diabetes mellitus.