The interleukin 6 -174 C/C genotype predicts greater rhinovirus illness.

Abstract

In adults and children with respiratory syncytial virus (RSV) infection, a polymorphism in the interleukin 6 (IL-6) promoter at position -174 predicts illness magnitude. In addition, polymorphisms in the interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) genes are associated with immune responsiveness and the frequency of complications. Here, the effect of these polymorphisms on illness and seroconversion during infection with rhinovirus type 39 (RV39) was evaluated. Seventy-two adults were genotyped for the selected polymorphisms, experimentally exposed to RV39, and followed to track infection, seroconversion, and symptoms and signs of illness. Regression analysis was used to determine whether these polymorphisms predicted seroconversion and illness magnitude in 57 infected subjects. The low-production IL-6 -174 phenotype (C/C genotype) was associated with greater symptom magnitudes, and the IFN-gamma phenotype +874 predicted the frequency of seroconversion. No relationship between the IL-10 or TNF-alpha polymorphisms and any measured outcome was documented. The concentration of IL-6 protein, as measured in nasal wash fluids from subjects, was positively correlated with symptom magnitude, but it was independent of the IL-6 -174 genotypes representing the high- and low-production phenotypes. These results document statistically significant associations between the IL-6 -174 and IFN-gamma +874 polymorphisms and specific responses to experimental RV39 infection. For the IL-6 -174 polymorphism, the results replicate those for experimental RSV infection.