Respiratory syncytial virus stimulates neutrophil degranulation and chemokine release

Neutrophil infiltration of the airways is a common finding in respiratory s yncytial virus (RSV) bronchiolitis. Neutrophil-derived chemokines and neutr ophil granule contents can cause further inflammation, hyperresponsiveness, and damage of the airways, In this study, peripheral blood neutrophils inc ubated with RSV (multiplicity of infection (MOI) = 10) induced IL-8, macrop hage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and myeloperoxidase (M PO) release. In contrast, LPS induced only chemokine but not MPO release, R SV-induced chemokine and MPO release was noncytotoxic as assessed by trypan blue exclusion. The mechanism of RSV-induced chemokine release was shown t o be transcription dependent since cytokine mRNA synthesis was increased wi th RSV stimulation and the process was inhibited by actinomycin-D. In addit ion, the effect of dexamethasone (dex) on mediator release was also studied . Dex significantly inhibited chemokine release but did not inhibit MPO rel ease; The mechanism of inhibition of the release of these chemokines is pro bably posttranscriptional since the mRNA synthesis was not inhibited by dex . We conclude that the release of chemokines (IL-8, MIP-1 alpha, MIP-1 beta ) and granule enzymes (MPO) by RSV-stimulated neutrophils may contribute to the pulmonary pathology in RSV bronchiolitis. These in vitro findings show ing that dex failed to consistently inhibit all the RSV-induced release of neutrophil inflammatory mediators may explain the variable efficacy of cort icosteroids in the treatment of RSV bronchiolitis.