INTERFERON-ALPHA ENHANCES NEUTROPHIL RESPIRATORY BURST RESPONSES TO STIMULATION WITH INFLUENZA-A VIRUS AND FMLP

Despite increasing therapeutic use of interferon (IFN)-alpha, its effe cts on human neutrophil function are not well characterized. In vitro preincubation of neutrophils with recombinant IFN-alpha and -gamma, tu mor necrosis factor (TNF), or granulocyte-macrophage colony-stimulatin g factor (GM-CSF) enhanced neutrophil respiratory burst responses to s timulation with influenza A virus (LAV) and FMLP. The enhancing effect s of IFNs were more subtle and required more prolonged incubation than those of TNF and GM-CSF. TNF and GM-CSF enhanced neutrophil binding o f IAV and neutrophil intracellular calcium and membrane depolarization responses to IAV or FMLP stimulation, while IFNs did not. Inhibitors of neutrophil tyrosine kinase activation and protein synthesis blocked IFN-alpha-induced enhancement of respiratory burst responses. In addi tion to its other well-characterized effects, IFN-alpha may protect ag ainst viral infection indirectly by promoting neutrophil respiratory b urst responses.