Glucocorticoid administration accelerates mortality of pneumovirus-infected mice.
The use of glucocorticoids for the treatment of symptoms associated with respiratory syncytial virus (RSV) infection has been questioned. To evaluate the sequelae of glucocorticoid administration in the setting of pneumovirus infection in vivo, hydrocortisone was administered to mice infected with pneumonia virus of mice (PVM), a pneumovirus and natural rodent pathogen that is closely related to RSV and replicates the signs and symptoms of severe human RSV infection. Results showed that hydrocortisone spared the pulmonary neutrophilia but resulted in ablation of the pulmonary eosinophilia, despite continued production of the relevant chemoattractant, macrophage inflammatory protein-1alpha. Hydrocortisone also led to diminished production of inducible nitric oxide synthase and accumulation of reactive nitrogen species in lung tissue and bronchoalveolar lavage fluid and diminished lymphocyte recruitment. PVM-infected mice responded to hydrocortisone with enhanced viral replication and accelerated mortality. These results suggest several mechanisms to explain why glucocorticoid therapy may be of limited benefit in the overall picture of pneumovirus infection.
Domachowske
J B
JB
Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University, Syracuse, NY, USA. domachoj@upstate.edu
Bonville
C A
CA
Ali-Ahmad
D
D
Dyer
K D
KD
Easton
A J
AJ
Rosenberg
H F
HF
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D004195:Disease Models, Animal; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D029122:Murine pneumonia virus / Q000302:isolation & purification / Q000502:physiology*; D011024:Pneumonia, Viral / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D018186:Pneumovirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000821:virology; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D006854:Hydrocortisone