Cytokine responses in porcine respiratory coronavirus-infected pigs treated with corticosteroids as a model for severe acute respiratory syndrome.
The effectiveness and potential immunosuppressive effects of anti-inflammatory glucocorticoids in the lungs of severe acute respiratory syndrome (SARS) patients are undefined. We treated porcine respiratory coronavirus (PRCV)-infected conventional pigs with the corticosteroid dexamethasone (DEX) as a model for SARS. Innate and Th1 cytokines in bronchoalveolar lavage (BAL) and serum were elevated in PRCV-infected pigs compared to controls, but were decreased after DEX treatment in the PRCV-infected, DEX-treated (PRCV/DEX) pigs. Although decreased in BAL, Th2 cytokine levels were higher in serum after DEX treatment. Levels of the proinflammatory cytokine interleukin-6 in BAL and serum were decreased in PRCV/DEX pigs early but increased later compared to those in phosphate-buffered saline-treated, PRCV-infected pigs, corresponding to a similar trend for lung lesions. PRCV infection increased T-cell frequencies in BAL, but DEX treatment of PRCV-infected pigs reduced frequencies of T cells; interestingly B and SWC3a(+) (monocytes/macrophages/granulocytes) cell frequencies were increased. DEX reduced numbers of PRCV-stimulated Th1 gamma interferon-secreting cells in spleen, tracheobroncheolar lymph nodes, and blood. Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression.
Zhang
Xinsheng
X
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave., Wooster, OH 44691, USA.
Alekseev
Konstantin
K
Jung
Kwonil
K
Vlasova
Anastasia
A
Hadya
Nagesh
N
Saif
Linda J
LJ
D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D018352:Coronavirus Infections; D016207:Cytokines / Q000276:immunology*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000009:adverse effects; D045722:Porcine Respiratory Coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000276:immunology*; D013552:Swine
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D003907:Dexamethasone