title: A pivotal role for interferon-gamma in protection against group A streptococcal skin infection.
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-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.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Raeder
authors.forename: L
authors.initials: L
authors.lastname: Barker-Merrill
authors.forename: T
authors.initials: T
authors.lastname: Lester
authors.forename: M D
authors.initials: MD
authors.lastname: Boyle
authors.forename: D W
authors.initials: DW
authors.lastname: Metzger
mesh_terms: D000818:Animals; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D013154:Spleen / Q000276:immunology; D013290:Streptococcal Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D013297:Streptococcus pyogenes
chemical_list: D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma