The modulating effects of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and immunoregulating cytokines IL-10 and transforming growth factor-beta (TGF-beta), on anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex.
We assessed the roles of proinflammatory cytokines IFN-gamma and TNF-alpha, and immunoregulatory cytokines IL-10 and TGF-beta in the modulation of the anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex (MAIC). First, both IFN-gamma and TNF-alpha significantly reduced the bacterial growth in macrophages, indicating that these cytokines participate in up-regulation of macrophage anti-MAIC function. Second, although MAIC-infected macrophages produced substantial amounts of IL-10 and TGF-beta, neutralization of endogenous IL-10 and TGF-beta with anti-IL-10 and anti-TGF-beta antibodies, respectively, did not affect the intracellular growth of MAIC in macrophages from mice with BcgS (MAIC-susceptible) or BcgI (MAIC-resistant) genotype, regardless of the virulence of test MAIC strains. The same result was also obtained for macrophages stimulated with IFN-gamma or TNF-alpha. Third, in MAIC-infected mice, the growth of organisms at the sites of infection (lungs and spleens) was not affected by administration of anti-IL-10 or anti-TGF-beta antibodies. These findings indicate that, in the case of mice, endogenous IL-10 and TGF-beta are essentially ineffective in down-regulating macrophage anti-MAIC functions not only in vitro but also in vivo.
Sano
C
C
Department of Microbiology and Immunology, Shimane Medical University, Japan. enarp@telecom.net.et
Sato
K
K
Shimizu
T
T
Kajitani
H
H
Kawauchi
H
H
Tomioka
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D015269:Mycobacterium avium Complex / Q000276:immunology*; D009500:Neutralization Tests; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D014376:Tuberculosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma