Effect of priming polymorphonuclear leukocytes with cytokines
(granulocyte-macrophage colony-stimulating factor [GM-CSF] and G-CSF) on
the host resistance to Streptococcus pneumoniae in chinchillas infected
with influenza A virus
JS Abramson and HR Hudnor
Department of Pediatrics, Bowman Gray School of Medicine of Wake Forest
University, Winston-Salem, NC 27157.
Patients infected with influenza A virus (IAV) are at increased risk for
bacterial superinfections, and this occurs in association with depressed
polymorphonuclear leukocyte (PMNL) function. Recently, we reported that in
vitro exposure of human PMNL to granulocyte-macrophage colony-stimulating
factor (GM-CSF) reverses IAV-induced cell dysfunction. The present study
used an established animal model of IAV infection to examine whether G-CSF
and/or GM-CSF can overcome IAV- induced PMNL dysfunction and thereby
prevent secondary infections. Preliminary studies determined a dosing
schedule of these cytokines that caused significant priming of chinchilla
PMNL. In subsequent studies, animals were inoculated intranasally with IAV
(day 1) followed 3 days later by Streptococcus pneumoniae, and administered
daily intraperitoneal injections with a cytokine or placebo on days 3
through 9. Animals had blood obtained on multiple occasions for PMNL
studies, and were followed-up for evidence of pneumococcal disease. Both
cytokines caused significant priming of the PMNL chemiluminescence response
and this was associated with reversal of the IAV-induced PMNL dysfunction.
However, neither cytokine decreased the incidence of pneumococcal disease.
Volume 83,
Issue 7,
pp. 1929-1934,
04/01/1994
Copyright © 1994 by The American Society of Hematology
