Lack of IL-10 synthesis by murine alveolar macrophages upon lipopolysaccharide exposure. Comparison with peritoneal macrophages

The central role of alveolar macrophages in the establishment of lipopolysa ccharide (LPS)-induced lung inflammation is well demonstrated. They produce and release numerous proinflammatory molecules, among which is tumor necro sis factor alpha (TNF-alpha), a cytokine responsible in part for the neutro philic alveolitis. Interleukin-10 (IL-10) produced by LPS-activated mononuc lear phagocytes is a major anti-inflammatory cytokine that down-regulates T NF-alpha synthesis. We studied the ability of murine alveolar macrophages t o produce IL-10 in vivo and in vitro, in response to LPS, Unexpectedly, the IL-10 protein was not detected in the whole lung and airspaces after LPS i ntranasal instillation, In addition, no IL-10 protein was found in supernat ants of isolated and LPS-stimulated alveolar macrophages, The lack of IL-10 synthesis was confirmed by the absence of specific RNA transcripts, By con trast and as expected, autologous peritoneal macrophages produced IL-10 upo n LPS challenge. Drugs that usually modify the TNF-alpha/IL-10 balance in f avor of IL-10 were used without success, Thus, maneuvers allowing an increa se in intracellular cAMP concentrations did not reverse this unexpected phe notype, Moreover, direct activation of protein kinase C with PMA was unable to trigger IL-10 formation by alveolar, by contrast to peritoneal, macroph ages, The current findings describe a specific phenotype for murine alveola r macrophages during LPS-induced inflammation.