Interferon inhibits agonist-induced cyclic AMP accumulation in human lymphocytes

Wheezing episodes often accompany viral respiratory infections. Viral pathogens are also known to induce interferon production. Cyclic AMP (cAMP) levels affect bronchial reactivity; therefore, we analyzed cAMP accumulation in human lymphocytes as a model to determine if interferon might influence the accumulation of this important intracellular mediator. After an overnight exposure to interferon in whole blood, a reduction in agonist-stimulated cAMP accumulation was demonstrated. Basal cAMP concentrations were equivalent in control and interferon-exposed lymphocytes from the same donor, but the response to isoproterenol and prostaglandin E1 was significantly reduced by 61 and 30%, respectively. The decreased responsiveness persisted in the presence of RO 20-1724, a phosphodiesterase inhibitor, indicating that the effect was in part due to a decrease in cAMP synthesis in intact cells. These results suggest that interferon may play a role in inducing or potentiating bronchospasm.