A pivotal role for interferon-gamma in protection against group A streptococcal skin infection.

Administration of exogenous recombinant interleukin-12 (rIL-12) either prophylactically or therapeutically provides significant protection against lethal group A streptococcal skin infection in a mouse model. Treatment of mice with rIL-12 before infection with group A streptococci induced expression of interferon-gamma (IFN-gamma) at the infection site. In vivo neutralization of IFN-gamma increased susceptibility to lethal infection and completely abrogated the protective effects of rIL-12. IFN-gamma knockout mice were also more susceptible to lethal infection. Although IL-12 treatment provided protection, higher doses induced significantly elevated levels of IFN-gamma transcription that were associated with increased susceptibility to lethal infection. These results support the hypothesis that IFN-gamma at the infection site is critical for protection but suggest that increased systemic levels are detrimental to survival after infection with group A streptococci.