Age-related differences in pulmonary cytokine response to respiratory syncytial virus infection: modulation by anti-inflammatory and antiviral treatment.
BACKGROUND
Respiratory syncytial virus (RSV) is the major cause of severe lower respiratory tract infection in infants and young children. Recently, RSV has also been recognized as a serious health risk in elderly individuals, but the pathogenesis of RSV infection in elderly individuals remains unknown.


METHODS
Dynamics of pulmonary cytokine response (including interferon- gamma , interleukin [IL]-4, IL-10, IL-6, monocyte chemoattractant protein-1, and growth-regulated oncogene [GRO] mRNA) during acute RSV infection were investigated in young (<2 months old) and aged (>9 months old) cotton rats (Sigmodon hispidus). Therapeutic treatments that diminish viral replication (antiviral antibody) and pulmonary inflammation (anti-inflammatory corticosteroid) in RSV-infected cotton rats were used to evaluate the contribution of virus replication and inflammation to the development of RSV disease with respect to age.


RESULTS
The time of the peak expression of the majority of cytokines was shifted with respect to age. Antiviral and anti-inflammatory treatments had a similar effect on cytokine expression in aged and young cotton rats. GRO mRNA transcripts were more abundant in the lungs of aged cotton rats.


CONCLUSIONS
The present study reports an age-related delay in the pulmonary cytokine response to RSV and an imbalance in chemokine production with respect to age and underscores different components of RSV pathogenesis with respect to their molecular signature.
Boukhvalova
Marina S
MS
Virion Systems, Inc., Rockville, MD 20850, USA. marinab@virionsystems.com
Yim
Kevin C
KC
Kuhn
Katie H
KH
Hemming
John P
JP
Prince
Gregory A
GA
Porter
David D
DD
Blanco
Jorge C G
JC
D000375:Aging / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D008168:Lung / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016205:Sigmodontinae
D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D016207:Cytokines; D012333:RNA, Messenger