Interferon-γ increases IL-12 mRNA expression and attentuates allergic late-onset airway responses in the Brown Norway rat

Interferon gamma is a T-helper cell (Th)-1-type cytokine that has been suggested to inhibit the development of an atopic Th2-type profile of cytokine expression, The aim of this study was to investigated the effect of exogenous rat interferon gamma on antigen-induced airway responses, and on Th1 and Th2-type cytokine messenger ribonucleic acid (mRNA) expression in the Brown Norway rat. Rats were actively sensitized to ovalbumin and 14 days later underwent an aerosolized ovalbumin challenge. Animals were intratracheally administered either interferon gamma (3,000 U) or control solvent 30 min prior to, and 2 and 4 h following, antigen challenge. Lung resistance was monitored over an 8-h time period. Using in situ hybridization and immunocytochemistry, the levels of Th1- (interleukin-12) and Th2-type (interleukin-4 and -5) cytokine mRNA, and major basic protein expression in the bronchoalveolar lavage fluid of these rats 8 h after ovalbumin challenge were also determined. Administration of interferon gamma attenuated the development of the late-onset airways response in ovalbumin-sensitized antigen-challenged rats (p<0.05), The expression of interleukin-4 and -5 mRNA in the bronchoalveolar lavage fluid of interferon gamma treated rats was significantly attenuated compared to ovalbumin-challenged saline-treated controls (p<0.001). This was accompanied by a significant increase in the expression of interleukin-12 mRNA, and a reduction in eosinophil numbers. Intratracheal administration of interferon gamma modulates the allergic late-onset airways response in rats, and this is associated with a reduction in the expression of T-helper cell 2-type cytokines and an increase in interleukin-12 messenger ribonucleic acid expression within the airways, The present results support a role for interferon gamma in the pathophysiology of acute allergic airway responses, possibly by virtue of its ability to modulate T-helper cell 1- 2-type cytokine expression within the lungs.