Effect of indomethacin on the modulation of Mycobacterium avium growth in human macrophages by interferon gamma, retinoic acid and 1,25(OH)2-vitamin D3.

A virulent strain of Mycobacterium avium was grown actively inside human adherent peripheral blood monocyte-derived macrophages with enhanced synthesis of prostaglandin E2 (PGE2). We therefore decided to investigate if the inability of human macrophages to control M. avium infection could be reversed using various immunomodulators, i.e. retinoic acid (RA), 1,25 dihydroxyvitamin D3 (D3) and interferon gamma (IFN gamma) alone or in combination, and whether this reversal was further potentiated by the addition of indomethacin (IND), a potent inhibitor of PGE2 biosynthesis. Among the various immunomodulators employed, only RA alone or in association with D3 or both D3 and IFN gamma were able to induce a clear mycobacteriostatic effect, which was further potentiated by IND. Our data suggest that immunosuppressive pathways induced in macrophages infected by M. avium result partly from an increased synthesis of PGE2 occurring soon after infection.