[Effects of various steroidal and non-steroidal anti-inflammatory drugs on in-vitro IL-10 production of murine peritoneal macrophages infected with Mycobacterium avium complex].
In murine infections due to Mycobacterium avium complex (MAC), bacterial regrowth of the pathogens is frequently encountered in the relatively late phase of infection even in mice receiving daily treatments with antimicrobial agents including rifamycins and macrolides. In this case, the bacterial regrowth is usually accompanied by concomitant increase in the tissue levels of IL-10 and transforming growth factor-beta (TGF-beta), well known immunosuppressive cytokines. In this context, it is of interest to note recent findings that steroidal anti-inflammatory drugs up-regulate TGF-beta production from T lymphocytes, thereby suggesting participation of immunosuppressive cytokines in the expression of their anti-inflammatory activity. In this study, we examined the effects of various anti-inflammatory drugs including glucocorticoids and non-steroidal anti-inflammatory drugs (NSAID) on in-vitro IL-10 production of murine peritoneal macrophages (M phi s) infected with MAC organisms. When the IL-10 production by MAC-infected M phi s was measured in terms of protein and mRNA expression of the cytokine using ELISA and RT-PCR assays, the following results were obtained. First, the IL-10 production into M phi culture fluids was temporarily increased around days 1 to 3, thereafter gradually declined, and returned to normal by day 14. Secondly, IL-10 mRNA expression of M phi s was rapidly induced after MAC-infection and the maximum level of the mRNA expression was achieved at 2 hr. Thereafter, IL-10 mRNA expression ceased rapidly and returned to normal by 24 hr. Thirdly, the majority of test anti-inflammatory drugs, not only glucocorticoids but also NSAID, were found to up-regulate the IL-10 production of MAC-infected M phi s, suggesting some possible roles of IL-10 in the expression of the anti-inflammatory activities of these agents.
Shimizu
T
T
Department of Microbiology and Immunology, Shimane Medical University.
Sano
C
C
Sato
K
K
Tomioka
H
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium; D015270:Mycobacterium avium-intracellulare Infection / Q000378:metabolism; D013256:Steroids
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013256:Steroids; D016753:Interleukin-10