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.
Raeder
R H
RH
Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio, USA.
Barker-Merrill
L
L
Lester
T
T
Boyle
M D
MD
Metzger
D W
DW
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
D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma