Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses.
We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.
Department of Medicine, East Carolina University School of Medicine, Greenville, NC 27858, USA.
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Lam
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Bouchard
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Sigounas
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Holbert
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Metzger
D000109:Acetylcholine / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology
D000276:Adjuvants, Immunologic; D000485:Allergens; D016207:Cytokines; D018664:Interleukin-12; D007073:Immunoglobulin E; D000109:Acetylcholine