Modulation of immune responses in murine pulmonary histoplasmosis.
The influence of endogenous interleukin (IL)-12 on the course of pulmonary histoplasmosis was examined in naive and immune mice. All naive animals pretreated with anti-IL-12 monoclonal antibody (MAb) died by day 14. All mice died when anti-IL-12 MAb was initiated as late as postinfection day 3. Unlike those of controls, lungs of naive mice given anti-IL-12 MAb had depressed levels of interferon (IFN)-gamma and increased tumor necrosis factor (TNF)-alpha. The 2 groups had similar IL-4 levels. Administration of anti-IL-4 MAb rescued mice from the inimical effects of anti-IL-12 MAb. Survival of mice given both anti-IL-12 and anti-IL-4 MAb was associated with a blunted TNF-alpha response. In reinfection histoplasmosis, treatment with anti-IL-12 MAb did not alter survival. Fungus burden in lungs, livers, and spleens differed at week 2, but not at week 1, of infection. Thus, endogenous IL-12 is critical for optimal generation of a protective immune response in pulmonary histoplasmosis.
Allendoerfer
R
R
Division of Infectious Diseases, University of Cincinnati College of Medicine, VA Medical Center, Ohio 45267-0560, USA.
Biovin
G P
GP
Deepe
G S
GS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis; D006660:Histoplasmosis / Q000276:immunology* / Q000473:pathology; D018664:Interleukin-12 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D008168:Lung / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats
D000911:Antibodies, Monoclonal; D016207:Cytokines; D018664:Interleukin-12; D015847:Interleukin-4