Human Infant Respiratory Syncytial Virus (RSV)–Specific Type 1 and 2 Cytokine Responses Ex Vivo during Primary RSV Infection

Abstract

Respiratory syncytial virus (RSV) infection is the most common respiratory viral infection resulting in hospitalizations in infants worldwide. Illness severity is likely multifactorial; however, unlike other viral infections, both type 1 and type 2 cytokine responses have been implicated in severe disease. We measured RSV-specific cytokine responses ex vivo during primary RSV infection in the blood of 18 infants with polymerase chain reaction-confirmed RSV infection. To focus on primary RSV infection, subjects were all<9 months old. RSV-specific cytokine responses were measured at 3 time points during acute primary RSV infection and at 1 memory time point 3-6 months later. RSV-specific interferon (IFN)- gamma responses were detected in 10 of 18 of infants. Infants with mild disease had higher RSV-specific IFN- gamma memory responses than did those with moderate or severe disease. No consistent correlations between RSV-specific IFN- gamma responses and corticosteroid administration were observed. RSV-specific interleukin (IL)-4 or IL-5 responses to primary RSV infection were detectable in 5 of 18 and 8 of 15 infants, respectively. During primary RSV infection, many infants demonstrated RSV-specific IFN- gamma responses. The strongest IL-4 and IL-5 responses were detected in 3 infants with severe disease, suggesting that type 2 responses may contribute to the pathogenesis of severe disease.