Interleukin-12 prevents antigen-induced eosinophil recruitment into mouse airways.
Interleukin-12 (IL-12) is a key cytokine that promotes Th1-type cell-mediated immunity and inhibits Th2-type responses. We have previously shown that antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by Th2-type CD4+ T cells that produce IL-5. Therefore, to determine whether IL-12 regulates antigen-induced eosinophil recruitment into the airways, we studied the effect of recombinant murine IL-12 on antigen-induced eosinophil infiltration into the tracheas of sensitized mice, and also the effect of IL-12 on IL-5 and interferon-gamma (IFN-gamma) levels in bronchoalveolar lavage fluid (BALF) from the mice. The intraperitoneal administration of recombinant IL-12 (rIL-12) inhibited antigen-induced eosinophil infiltration into the mouse trachea in a dose-dependent manner. The administration of rIL-12 suppressed IL-5 levels but enhanced IFN-gamma levels in the BALF of the mice after antigen inhalation. The administration of rIL-12 also decreased in vitro antigen-induced IL-4 and IL-5 production, but not IFN-gamma production, in spleen cells of the mice. Furthermore, pretreatment with anti-IFN-gamma monoclonal antibody prevented the IL-12 inhibition of antigen-induced eosinophil infiltration into the tracheas of the mice. These results indicate that IL-12 downregulates antigen-induced eosinophil recruitment into the airways by inhibiting IL-5 production in sensitized animals.
Department of Internal Medicine, Chiba University School of Medicine, Japan.
I
I
Iwamoto
K
K
Kumano
M
M
Kasai
K
K
Kurasawa
A
A
Nakao
D000818:Animals; D000941:Antigens / Q000187:drug effects* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014132:Trachea / Q000187:drug effects* / Q000276:immunology
D000941:Antigens; D015848:Interleukin-5; D018664:Interleukin-12; D007371:Interferon-gamma