Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice.
Pretreatment of lipopolysaccharide (LPS)-responder C57BL/10ScSn mice with killed Propionibacterium acnes enhanced tumor necrosis factor alpha (TNF-alpha) production and lethality in response to a subsequent challenge with LPS. Sensitization to LPS increased with time of pretreatment and reached its maximum after 7 days. Sensitization was paralleled by gamma interferon (IFN-gamma) production that was detectable from day 3 onward. In contrast, a similar P. acnes pretreatment of LPS-nonresponder C57BL/10ScCr mice had no apparent effect on their high resistance to LPS. Challenge with LPS at any time during the 7-day period after P. acnes treatment led to no detectable TNF-alpha formation and caused no lethal effects. The absence of sensitization in C57BL/10ScCr mice was paralleled by an absence of IFN-gamma production. Administration of monoclonal IFN-gamma antibodies in C57BL/10ScSn mice up to day 3 of P. acnes treatment completely inhibited the overproduction of TNF-alpha by LPS. Anti-IFN-gamma administered later than day 3 had only a partial, although significant, inhibitory effect. Injection of appropriate amounts of anti-IFN-gamma also abolished the development of hypersensitivity to the lethal action of LPS. The effect of exogenously administered IFN-gamma on LPS sensitivity (e.g., TNF-alpha production, lethal effects) was studied in LPS-responder and nonresponder mice. Administration of murine recombinant IFN-gamma increased the sensitivity of C57BL/10ScSn mice to LPS and established LPS responsiveness in LPS-nonresponder C57BL/10ScCr and C3H/HeJ mice. The data provide evidence that IFN-gamma mediates the sensitization towards LPS induced by P. acnes.
Katschinski
T
T
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Galanos
C
C
Coumbos
A
A
Freudenberg
M A
MA
D000818:Animals; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011425:Propionibacterium acnes / Q000276:immunology*; D051381:Rats; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma