Transforming growth factor beta (TGF-b1) plays a detrimental role in the progression of experimental Mycobacterium avium infection; in vivo and in vitro evidence.

BALB/c mice were infected with 10(5) colony forming units (cfu) of Mycobacterium avium TMC 702 i.v. and the growth of the inoculum followed in the spleens of control mice. Other infected mice given weekly doses of 1 microgram of TGF-b1 or weekly doses of 2 mg of a rabbit antiserum against mouse TGF-b1 were evaluated for their resistance to M. avium TMC 702. Growth of M. avium in the spleens of mice given repeated doses of TGF-b1 (1 microgram weekly) was significantly higher than in the spleens of control mice starting at day 40 of infection. Similarly, growth of M. avium was significantly diminished (0.7 log difference at 80 days) in mice given infusions of anti-TGF-b1 (2 mg weekly). Macrophage activation status was similar in the three groups of mice, as seen by a comparable release of superoxide anion (O2-) and hydrogen peroxide (H2O2) by peritoneal macrophages of infected mice. However, TGF-b1-pulsed peritoneal macrophages were found to be more permissive for M. avium growth in vitro than control macrophage monolayers. Overall, these results suggest that TGF-b1 plays a detrimental role in the progression of experimental M. avium infections, by an unclear mechanism.