A Pivotal Role for Interferon‐γ in Protection against Group A Streptococcal Skin Infection

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Abstract
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-γ (IFN-γ) at the infection site. In vivo neutralization of IFN-γ increased susceptibility to lethal infection and completely abrogated the protective effects of rIL-12. IFN-γ knockout mice were also more susceptible to lethal infection. Although IL-12 treatment provided protection, higher doses induced significantly elevated levels of IFN-γ transcription that were associated with increased susceptibility to lethal infection. These results support the hypothesis that IFN-γ at the infection site is critical for protection but suggest that increased systemic levels are detrimental to survival after infection with group A streptococci.

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