Cytokines in antibacterial resistance: possible applications for immunomodulation.
Acquired resistance to intracellular bacteria is primarily mediated by T cells which--by secreting multiple interleukins (ILs)--activate antimicrobial activities in mononuclear phagocytes. Experimental infection of mice with Listeria monocytogenes and Mycobacterium bovis has helped to clarify the role of ILs in antimicrobial infection. These studies revealed: 1) application of IFN-gamma reduces the number of L. monocytogenes and treatment with anti-IFN-gamma antibodies worsens listeriosis; 2) in vitro, tuberculostatic and listericidal macrophage functions are activated by IFN-gamma, IL-4, and IL-6; 3) tumor necrosis factor (TNF) synergizes with IFN-gamma; 4) treatment with anti-TNF antibodies worsens listeriosis and interferes with M. bovis-induced granuloma formation; 5) concomitant application of mycobacterial products and TNF induces necrotic reactions. In humans at least some effects of IFN-gamma on macrophages may be mediated via 1,25-dihydroxyvitamin D3. These findings illustrate the multifaceted role of ILs in antimicrobial resistance and point to a central role of IFN-gamma.
Kaufmann
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Department of Medical Microbiology and Immunology, University of Ulm, Federal Republic of Germany.
Flesch
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D000818:Animals; D001685:Biological Factors / Q000502:physiology* / Q000627:therapeutic use; D016207:Cytokines; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D007110:Immunity, Active / Q000502:physiology*; D007111:Immunity, Cellular / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D001685:Biological Factors; D016207:Cytokines