Adjuvant treatment increases the resistance to Mycobacterium avium infection of mycobacteria-susceptible BALB/c mice.

We have investigated the effect of inflammation on host resistance against infection by Mycobacterium avium, an atypical mycobacteria species that is responsible for life-threatening opportunistic infections in AIDS patients. Inflammation was induced in BALB/c mice by two intraperitoneal injections of mineral oil (Freund's incomplete adjuvant, FIA). The BALB/c strain was chosen because it is naturally susceptible to Myco. avium infection. One week after the second FIA injection, the BALB/c mice were infected intravenously with 2.6 x 10(6) Myco. avium bacilli; at this time, the mice showed systemic granulocytosis because of the FIA injections. The kinetics of the murine infection was determined during 3 months by quantification of Myco. avium loads in the major target organs (liver and spleen) of the mycobacteria. The FIA treatment resulted in a significant decrease in the growth of Myco. avium in the infected BALB/c mice. This enhancement in host resistance to Myco. avium infection lasted for 2-3 months. In contrast with BALB/c animals, C3H mice (naturally resistant to Myco. avium infection) did not show an increased anti-Myco. avium action in association with the FIA treatment. The antimycobacterial effect of the FIA injections in BALB/c mice was compared with that produced by the injection of mycobacterial antigens (heat-killed Myco. tuberculosis) added to the mineral oil (i.e. Freund's complete adjuvant, FCA). The FCA treatment resulted in strong and sustained enhancements in the microbicidal capacities of BALB/c, and also of C3H mice. Data obtained with mutant athymic BALB/c mice revealed that the anti-Myco. avium effect of the FCA treatment was T cell-dependent. Our results indicate that: (i) non-immune inflammatory stimulation (FIA) of Myco. avium-susceptible hosts is able to cause a significant, albeit transient, increase in the resistance to Myco. avium infection; (ii) this protective effect is enhanced if heat-killed mycobacteria are added to the phlogistic agent (FCA), i.e. if a T cell-dependent response is induced; and (iii) systemic increase in the number of circulating granulocytes may help host defence against Myco. avium infection.