Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection

Background: It has been claimed that an early respiratory syncytial virus (RSV) infection can induce asthma and recurrent wheezing. Objective: We addressed the question of whether infants contracting an early RSV infection differ from healthy children in their cytokine production at birth. Methods: In a prospective cohort study cord blood samples were collected from 1084 newborns during autumn 2001. Of 47 of these newborns with subsequent virologically confirmed RSV infection before 6 months of age, 24 had enough cells for stimulation in cord blood samples (14 of those were hospitalized). Twenty-eight children had other respiratory virus infections (16 with enough cells), and samples from 48 healthy children of the 1084 total served as control specimens. Stimulated cytokine production of mononuclear cells was measured. The responses in the groups were evaluated by means of factor analysis. Results: The infants hospitalized for RSV infection had higher LPS-stimulated combined IL-6 and IL-8 responses than the infants treated as outpatients (P = .005) or the healthy control subjects (P = .02). The hospitalized patients with RSV showed lower IL-10, IL-2, IL-4, IL-5, and IL-10 responses than those treated as outpatients (P = .02). High IL-6 and IL-8 responsiveness predicted a severe RSV infection (odds ratio, 2.20; 95% CI, 1.17-4.14; P = .01). The unstimulated cytokine responses at birth did not differ between the patients and healthy control subjects. Conclusion: The results suggest that natural differences in innate immunity predispose children to severe RSV infection rather than the infection modifying immune responses in childhood. (J Allergy Clin Immunol 2009;124:52-8.)