SEROTYPE-DEPENDENT INDUCTION OF PULMONARY NEUTROPHILIA AND INFLAMMATORY CYTOKINE GENE-EXPRESSION BY REOVIRUS

Reovirus type 3 Dearing (T3D) causes a prominent neutrophil influx, su bstantially greater than seen with reovirus type 1 Lang (T1L) in a rat model of viral pneumonia, We sought to measure reovirus-mediated incr eases in chemokine mRNA expression in pulmonary cells. We found that t he neutrophilia induced by T1L and T3D infection in vivo correlated di rectly with increased levels of chemokine mRNA expression in T3D-infec ted compared with those of T1L-infected lungs, In vitro, reovirus-infe cted normal alveolar macrophages (AMs) and the rat AM cell line NR8383 expressed greater levels of macrophage inflammatory protein 2, KC, an d tumor necrosis factor alpha mRNA, A synergism between reovirus and l ipopolysaccharide was also detected for macrophage inflammatory protei n 2 and KC mRNA expression. Tumor necrosis factor protein secretion wa s also increased to a greater extent by T3D than by T1L in primary rat AMs and the NR8383 cells. We conclude that the virus-mediated inflamm atory cytokine induction suggests a role for these cytokines in the ne utrophil influx observed in the rat reovirus pneumonia model.