Association of cytokine responses with disease severity in infants with respiratory syncytial virus infection

Aim: To explore the relationship between cytokine responses and severity of respiratory syncytial virus (RSV) infection in infants. Methods: Intracellular interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) expression in peripheral blood CD3(+) and CD8(+) lymphocytes was measured by four-colour flow cytometry. Serum IL-12, IL-4 and IFN-gamma levels were also determined by enzyme-linked immunosorbent assay. Results: The frequency of IL-4 and IFN-gamma expression in CD3(+)CD8(-) cells was the same in RSV-infected, non-RSV-infected and control infants and in those with RSV bronchiolitis or RSV pneumonia, indicating that no Th2 predominance exists in the acute phase of RSV infection and RSV bronchiolitis. Furthermore, RSV-infected infants had a more frequent IFN-gamma expression in CD3(+)CD8(+) cells than controls, and they also showed a much lower serum IL-4/IFN-gamma ratio because of decreased IL-4 and elevated IFN-gamma, the latter being most prominent in RSV bronchiolitis. The serum IL-12 level in RSV-infected infants was the same as in control infants, while those with non-RSV infections had a much higher level. Serum IL-12, IFN-gamma and frequency of IFN-gamma expression in CD3(+)CD8(+) cells in mild RSV infection were much higher than in controls, while no difference existed between severe cases and controls. Conclusion: Type 2 cytokine predominance was not found in the acute phase of RSV infection and RSV bronchiolitis, but both were accompanied by enhanced production of IFN-gamma and a much higher serum IFN-gamma level than in healthy controls, especially in those with RSV bronchiolitis, suggesting a role in causing airway obstruction. IFN-gamma and IL-12 may also play a protective role in RSV infections by diminishing viral replication, and high levels of IL-12 and IFN-gamma may be associated with lessening of the severity of infection.