Interleukin 10 Inhibits Alveolar Macrophage Production of Inflammatory Mediators Involved in Adult Respiratory Distress Syndrome

• Published in: The Journal of surgical research 1998-10, Vol.79 (2), p.179-184
• Main Authors: Lo, Chong-Jeh, Fu, Minjuan, Cryer, H.Gill
• Format: Article
• Language: English
• Subjects: A23187; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Blood Coagulation Factors - biosynthesis; Calcium - metabolism; Emergency and intensive respiratory care; Enzyme Activation - physiology; Humans; IL-10; Infant, Newborn; Inflammation Mediators - antagonists & inhibitors; Intensive care medicine; Interleukin-10 - pharmacology; Intracellular Membranes - metabolism; Lipopolysaccharides - pharmacology; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Male; Medical sciences; Osmolar Concentration; PCA; PGE2; PMA; protein kinase C; Protein Kinase C - metabolism; Rabbits; Respiratory Distress Syndrome, Newborn - metabolism; Respiratory Distress Syndrome, Newborn - pathology; TNF; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1998.5418

Background.Adult respiratory distress syndrome (ARDS) causes severe morbidity and mortality in trauma patients. One potential method to attenuate the lung injury is to inhibit alveolar macrophage production of proinflammatory mediators. The purpose of this study was to investigate the cellular mechanism of interleukin 10 (IL-10) inhibition on LPS-stimulated macrophage (Mφ). We hypothesized that IL-10 inhibited phospholipase C signal pathways in Mφ. IL-10 inhibition would be restored by calcium ionophores and protein kinase C (PKC) activation. Methods.Rabbit alveolar Mφ were obtained by bronchoalveolar lavage. Mφ were treated withEscherichia coliLPS (10 ng/ml) in the presence of various concentrations of human IL-10. Cell lysates and supernatant were analyzed for proagulants (PCA) and tumor necrosis factor (TNF), respectively. TNF mRNA expression of alveolar Mφ was also measured by Northern Blot assay. Macrophage PGE2production was measured by ELISA. Results.IL-10 inhibited the production of both TNF and PCA by LPS-stimulated Mφ. In addition, IL-10 also reduced TNF mRNA expression. Similarly, PGE2production by LPS-stimulated Mφ was also attenuated by IL-10. An increase in the intracellular [Ca2+] induced by A23187 failed to reverse this IL-10-mediated inhibition. In comparison, phorbol myristate acetate, a protein kinase C (PKC) activator, restored TNF and PCA production despite the presence of IL-10. Conclusions.IL-10 inhibits Mφ production of inflammatory mediators. This inhibition is, at least in part, mediated by modulating the PKC activity.