Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

Tropical Pulmonary Eosinophilia (TPE) is a severe Set-in of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increase d filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of rec ombinant murine IL-12 modulated the T helper (Th) response in the lungs fro m Th2- to Th1-like, with elevated IFN-gamma, and decreased IL-4 and IL-5 pr oduction. Consistent with this shift in cytokine response, antigen-specific IgC2a was elevated and IgG1 and total serum IgE were decreased In addition , eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Impo rtantly, IL-12 suppressed airway hyperresponsiveness compared with saline-i njected control animals. Taken together, these data clearly demonstrate tha t by modulating Th associated cytokine production, IL-12 down-regulates fil aria-induced lung immunopathology.