Stress and influenza viral infection: modulation of proinflammatory cytokine responses in the lung.

Viral infection of the respiratory tract induces a complex series of cellular and molecular events leading to immunological responses designed to terminate viral replication. Anti-viral immunity involves natural resistance mechanisms that overlap and modulate the development of the subsequent adaptive immune responses. An experimental murine infection with influenza A/PR8 virus was used to examine the effects of stress-induced activation of the nervous and endocrine systems on components of innate immunity. Proinflammatory cytokine responses (IL-1alpha, IL-6 and TNFalpha) were measured in the lungs during an influenza A/PR8 viral infection. For activation of the nervous and endocrine systems, restraint stress (RST) was applied prior to and during infection. Following infection, IL-1alpha increased transiently, while elevated IL-6 persisted; TNFalpha was not detected. RST suppressed virally-induced IL-1alpha, while IL-6 was unaffected. These data demonstrate differential regulation of proinflammatory cytokines by stress. The mechanism underlying suppression of the lung IL-1alpha in stressed mice is currently unknown; its downregulation may contribute to increased viral pathogenesis in stressed individuals.