INTERLEUKIN (IL)-12 DEFICIENCY IN SUSCEPTIBLE MICE INFECTED WITH MYCOBACTERIUM-AVIUM AND AMELIORATION OF ESTABLISHED INFECTION BY IL-12 REPLACEMENT THERAPY

Mycobacterium avium is an intracellular microorganism that infects and multiplies within macrophages. Cell-mediated immunity plays an import ant role in host defense, and interleukin (IL)-12, which is produced m ainly by macrophages, is critical for its development. In a mouse mode l of disseminated M. avium infection, genetically susceptible BALB/c m ice had increased mycobacterial growth and decreased IL-12 expression and developed large and numerous granulomas. In contrast, resistant DB A/2 mice exhibited reduced mycobacterial burden with increased IL-12 e xpression and developed fewer and smaller granulomas. In susceptible m ice with established M. avium infection, IL-12 replacement therapy res ulted in persistent reduction of mycobacterial burdens, IL-12 itself, however, could not inhibit mycobacterial growth in vitro. By enhancing host defenses, IL-12 exerts a potent mycobactericidal activity in viv o with low toxicity. This suggests that IL-12 replacement therapy is r ational for M. avium infection in susceptible hosts.