Cytokine gene polymorphisms moderate responses to respiratory syncytial virus in adults.

Immune responses and illness severity during viral upper respiratory infections may be influenced by the local elaboration of cytokines. Cytokine gene polymorphisms moderate immune responses and severity of illness in various inflammatory and infectious diseases. We performed cytokine genotyping on 29 adults experimentally inoculated with respiratory syncytial virus (RSV) to determine whether specific cytokine gene polymorphisms are associated with immune responses or illness severity. DNA was extracted from leukocytes and assayed for TNF-alpha, IFN-gamma, IL-6, IL-10 and TGF-beta1 genotypes using polymerase chain reaction-sequence-specific primer technology. Outcomes consisted of baseline and convalescent RSV-specific serum IgG and nasal IgA titers, nasal secretion weights, nasal, throat and general symptom scores, and nasal cytokine protein levels. IFN-gamma genotype was directly related with the frequency of subjects having at least a four-fold increase in RSV-specific serum IgG and TNF-alpha genotype was inversely associated with the frequency of subjects having at least a twofold increase in RSV-specific nasal IgA. Additionally, IL-6 genotype was predictive of certain measures of illness expression, while IFN-gamma genotype predicted IL-1 protein levels, and TNF-alpha genotype predicted IL-6 and IL-8 protein levels in nasal lavage fluids. There were no associations between IL-10 or TGF-beta1 and any of the outcome parameters. These results suggest that certain cytokine gene polymorphisms moderate immune responses and illness severity in adults experimentally exposed to RSV.