Abstract
Rhinovirus and respiratory syncytial virus (RSV) are the most prevalent inducers of upper respiratory tract infections (URTI) in infants and may stimulate immune maturation. To estimate the amount of immune stimulation, nasal immune responses were examined during rhinovirus and RSV-induced URTI in infants. Nasal brush samples were taken from infants (2-26 months; 57% atopic family) with rhinovirus-induced URTI (N=20), with RSV-induced URTI (N=7), and with rhinovirus-induced rhinitis (N=11), from children with asymptomatic rhinovirus infection (N=7) and from eight non-infected children. Numbers of nasal brush cells positive for Th1-, Th2-, regulatory and proinflammatory cytokines were measured by immunohistochemistry or by measuring protein levels using a cytometric bead array analysis. During rhinovirus and RSV-induced URTI, fewer regulatory cytokine IL-10 positive cells were found compared to non-infected children. This fall was accompanied by an increase in levels of the Th1 cytokine TNFalpha. IL-10 responses were inversely related to TNFalpha responses. No enhanced responses were observed for IFNgamma, IL-12 and IL-18. Cytokine responses were comparable in children with rhinovirus-induced URTI and in children with rhinitis, while responses in asymptomatic rhinovirus-infected children were located between those for symptomatic and asymptomatic rhinovirus-infected children. Cytokine responses did not depend on the age of the child or atopy in the family. In conclusion, reduced nasal IL-10 responses during URTI in infants could facilitate the induction of a TNFalpha response. TNFalpha in turn could replace the immature production of IL-12, IL-18 and IFNgamma during URTI to induce an effective clearance of the viral infection and which could stimulate the maturation of Th1 cytokine production in infancy.