Interleukin-6−174 and Tumor Necrosis Factor α−308 Polymorphisms Enhance Cytokine Production by Human Macrophages Exposed to Respiratory Viruses

Interleukin-6−174 (IL-6−174) and tumor necrosis factor α−308 (TNFα−308) are high-cytokine-producing genotypes that are known to increase the susceptibility to infectious diseases, but their influence on cytokine production induced by respiratory viruses is unknown. We exposed human monocyte-derived macrophages from IL-6−174, TNFα−308, and normal genotype donors to different respiratory viruses. Respiratory syncytial virus (RSV) stimulation was associated with higher IL-6 concentrations in IL-6−174 donors than in normal donors (P = 0.015); 2 of 7 (29%) polymorphic donors were poor responders compared with 6 of 7 (86%) normal donors (P = 0.002). Adenovirus, influenza virus, and RSV stimulations were associated with higher TNFα concentrations in TNFα−308 donors than in normal donors (P = 0.03, <0.01, <0.01). A similar trend was seen with rhinovirus stimulation, but this was not significant. These results show that IL-6−174 and TNFα−308 gene polymorphisms lead to enhanced production of the respective cytokine...