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.