Epithelial cells infected with respiratory syncytial virus are resistant to the anti-inflammatory effects of hydrocortisone.
In this work we continue our study of the biochemical responses of respiratory epithelial cells to infection with human paramyxovirus pathogens. In our earlier studies, we detected elevated concentrations of the proinflammatory chemokines MIP-1alpha and IL-8 in upper and lower respiratory tract secretions from patients infected with respiratory syncytial virus (RSV). Here we demonstrate the same trend for individuals infected with parainfluenza virus (PIV), with elevated concentrations of MIP-1alpha and IL-8 (means of 309 +/- 51 and 2280 +/- 440 pg/ml/mg protein, respectively) detected in nasal wash samples from 17 patients with culture-positive PIV. Similar to our findings with RSV, cells of the HEp-2 epithelial line and primary cultures of human bronchial epithelial cells respond to PIV infection with production and release of both MIP-1alpha and IL-8. Addition of the glucocorticoid anti-inflammatory agent hydrocortisone (200-1000 ng/ml) attenuated the production of MIP-1alpha and IL-8 in PIV-infected cells while having minimal to no effect on the production of these mediators from cells infected with RSV. Neither virus infection resulted in a change in the total cellular concentration of glucocorticoid receptors, nor did hydrocortisone exert any differential effect on viral replication. As repression of chemokine production by epithelial cells is likely to result in diminished recruitment of proinflammatory leukocytes, these results may explain in part why glucocorticoid therapy reduces the symptoms associated with acute PIV infection, but have little to no effect in the overall outcome in the case of RSV.
Bonville
C A
CA
Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, New York, 13210, USA.
Mehta
P A
PA
Krilov
L R
LR
Rosenberg
H F
HF
Domachowske
J B
JB
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002675:Child, Preschool; D003470:Culture Media; D004351:Drug Resistance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D005260:Female; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007223:Infant; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D017817:Nasal Lavage Fluid / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000893:Anti-Inflammatory Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003470:Culture Media; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D006854:Hydrocortisone