Increased production of IFN-γ and cysteinyl leukotrienes in virus-induced wheezing

Background: An imbalance of production of T-helper lymphocyte cytokines, favoring overproduction of IL-4, is believed to be important in the pathogenesis of allergic asthma. However, less is known about the cytokine response in virus-induced wheezing, which is a major cause of morbidity in asthma. Objective: We undertook this study to determine the magnitude of IFN-gamma, IL-4 and IL-10, and leukotriene (LT) responses in infants and children with virus-induced wheezing, Methods: We measured the concentrations of IFN-gamma, IL-4 and IL-10, and cysteinyl LTs in respiratory secretions of 82 infants and young children during acute episodes of virus-induced wheezing. Control subjects were 47 infants and children with uncomplicated upper respiratory infections and 18 normal healthy infants. Results: Ratios of IFN-gamma to IL-4 were higher (due to increased quantities of IFN-gamma) in subjects with wheezing than in those with upper respiratory infection alone (P =.003). Quantities of LTs were also increased in wheezing subjects in comparison with those with upper respiratory infections (P =.003), There was a significant correlation between measured concentrations of IFN-gamma and LTs (correlation coefficient = .451, P =.007), Quantities of IL-4 were slightly suppressed in the wheezing groups. Conclusions: An imbalance favoring overproduction of IFN-gamma appears to be associated temporarily with virus-induced wheezing. A possible mechanism is the enhanced release of LTs from eosinophils or mast cells after sensitization by IFN-gamma.