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

Administration of exogenous recombinant interleukin-12 (rIL-12) either prop hylactically or therapeutically provides significant protection against let hal group A streptococcal skin infection in a mouse model. Treatment of mic e with rIL-12 before infection with group A streptococci induced expression of interferon-gamma (IFN-gamma) at the infection site. In vivo neutralizat ion of IFN-gamma increased susceptibility to lethal infection and completel y abrogated the protective effects of rIL-12, IFN-gamma knockout mice were also more susceptible to lethal infection. Although IL-12 treatment provide d protection, higher doses induced significantly elevated levels of IFN-gam ma transcription that were associated with increased susceptibility to leth al infection. These results support the hypothesis that IFN-gamma at the in fection site is critical for protection but suggest that increased systemic levels are detrimental to survival after infection with group A streptococ ci.