Roles of interleukin-12 and gamma interferon in murine Chlamydia pneumoniae infection

BALB/c and strain 129 mice infected intranasally with Chlamydia pneumoniae displayed a moderate-to-severe inflammation in the lungs and produced inter leukin-12 (IL-12), gamma interferon (IFN-gamma), tumor necrosis factor alph a (TNF-alpha), and IL-10, with peak levels on days 1 to 3 postinfection (p. i.), returning to basal levels by day 16 p.i. Anti-IL-12 treatment resulted in less-severe pathological changes but higher bacterial titers on days 3 and 7 p.i. By day 16 p.i., the inflammatory responses of control antibody-t reated mice subsided. The bacterial titers of both anti-IL-12- and control antibody-treated mice decreased within 3 weeks to marginally detectable lev els. Anti-IL-12 treatment significantly reduced lung IFN-gamma production a nd in vitro spleen cell IFN-gamma production in response to either C. pneum oniae or concanavalin A. In gamma-irradiated infected mice, cytokine produc tion was delayed, and this delay correlated with high bacterial titers in t he lungs. Following C. pneumoniae infection, 129 mice lacking the IFN-gamma receptor or chain gene (G129 mice) produced similar IL-12 levels and exhib ited similarly severe pathological changes but had higher bacterial titers than 129 mice. However, by day 45 p.i., bacterial titers became undetectabl e in both wild-type 129 and G129 mice. Thus, during C. pneumoniae lung infe ction, IL-12, more than IFN-gamma, plays a role in pulmonary-cell infiltrat ion. IFN-gamma and IL-12, acting mostly through its induction of IFN-gamma and Th1 responses, play an important role in controlling acute C. pneumonia e infection in the lungs, but eventually all mice control the infection to undetectable levels by IL-12- and IFN-gamma-independent mechanisms.