Effect of Th2 cytokine antagonist treatments on chemical-induced allergic response in mice.
To understand better the cellular and molecular mechanisms of chemical-induced occupational asthma, we examined the effects of the Th2 cytokine antagonists interferon-gamma (IFN-gamma), interleukin (IL)-12 and anti-IL-4 on the balance of the Th1/Th2 response induced by trimellitic anhydride (TMA) and phthalic anhydride (PA). Eight- to ten-week-old BALB/c mice were assigned to be exposed to either TMA or PA plus one of these Th2 cytokine antagonists. Both TMA (25% and 12.5% for sensitization and challenge, respectively) and PA (12.5% and 6.25% for sensitization and challenge, respectively) induced a Th2 response marked by an increasing production of IL-4 and IL-10 in the supernatants of ex vivo spleen cells cultured with concanavalin A and also of serum total IgE. Co-administration of IL-12 and antiIL-4 deviated these PA- or TMA-induced Th2 responses, as judged by an increasing serum total IgG2a production (up to 14-fold), associated with a slight decrease of IL-4 in three out of four experiments and of IL-10 in all four experiments. Co-administration of IFN-gamma, however, had only one weak effect. These findings suggest that the chemical-induced Th2-biased response may be diverted during an induction period by exogenous administration of the Th2 cytokine antagonists, particularly IL-12 and the anti-IL-4 antibody. These results would significantly enhance our understanding of the Th1/Th2 response induced by chemicals.
Ban
Masarin
M
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre, France. masarin.ban@inrs.fr
Hettich
Denise
D
D000276:Adjuvants, Immunologic; D000818:Animals; D000998:Antiviral Agents / Q000097:blood*; D004342:Drug Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000097:blood / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use; D015847:Interleukin-4 / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D007376:Interleukin-2; D010796:Phthalic Anhydrides; D018664:Interleukin-12; D015847:Interleukin-4; C015559:trimellitic anhydride; D007371:Interferon-gamma; C043103:phthalic anhydride