Interferon-gamma 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 sugg ested to inhibit the development of an atopic Th2-type profile of cytokine expression, The aim of this study was to investigated the effect of exogeno us rat interferon gamma on antigen-induced airway responses, and on Th1 and Th2-type cytokine messenger ribonucleic acid (mRNA) expression in the Brow n Norway rat. Rats were actively sensitized to ovalbumin and 14 days later underwent an a erosolized ovalbumin challenge. Animals were intratracheally administered e ither 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) cytokin e mRNA, and major basic protein expression in the bronchoalveolar lavage fl uid of these rats 8 h after ovalbumin challenge were also determined. Administration of interferon gamma attenuated the development of the late-o nset airways response in ovalbumin-sensitized antigen-challenged rats (p<0. 05), The expression of interleukin-4 and -5 mRNA in the bronchoalveolar lav age fluid of interferon gamma treated rats was significantly attenuated com pared to ovalbumin-challenged saline-treated controls (p<0.001). This was a ccompanied by a significant increase in the expression of interleukin-12 mR NA, and a reduction in eosinophil numbers. Intratracheal administration of interferon gamma modulates the allergic lat e-onset airways response in rats, and this is associated with a reduction i n the expression of T-helper cell 2-type cytokines and an increase in inter leukin-12 messenger ribonucleic acid expression within the airways, The pre sent results support a role for interferon gamma in the pathophysiology of acute allergic airway responses, possibly by virtue of its ability to modul ate T-helper cell 1- 2-type cytokine expression within the lungs.