Interleukin 10 inhibits alveolar macrophage production of inflammatory mediators involved in adult respiratory distress syndrome.
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 (Mphi). We hypothesized that IL-10 inhibited phospholipase C signal pathways in Mphi. IL-10 inhibition would be restored by calcium ionophores and protein kinase C (PKC) activation.


METHODS
Rabbit alveolar Mphi were obtained by bronchoalveolar lavage. Mphi were treated with Escherichia coli LPS (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 Mphi was also measured by Northern Blot assay. Macrophage PGE2 production was measured by ELISA.


RESULTS
IL-10 inhibited the production of both TNF and PCA by LPS-stimulated Mphi. In addition, IL-10 also reduced TNF mRNA expression. Similarly, PGE2 production by LPS-stimulated Mphi 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 Mphi production of inflammatory mediators. This inhibition is, at least in part, mediated by modulating the PKC activity.
Lo
C J
CJ
Department of Surgery, University of California, Los Angeles, California 90095-6904, USA.
Fu
M
M
Cryer
H G
HG
D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D016753:Interleukin-10 / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001779:Blood Coagulation Factors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011493:Protein Kinase C; D002118:Calcium