Induction of Allergen-specific IL-2 Responsiveness of Lymphocytes After Respiratory Syncytial Virus Infection and Prediction of Onset of Recurrent Wheezing and Bronchial Asthma

Background: In pediatric patients with bronchial asthma and/or atopic dermatitis, peripheral lymphocytes are activated if they are stimulated with the responsible antigen, resulting in induction of responsiveness to IL-2. Because some nursing infants experience recurrent wheezing after respiratory syncytial virus (RSV) infection, attention is being directed to progression of the disease to bronchial asthma.

Objective: The study was designed to elucidate the mechanism of the onset of allergic diseases after RSV infection.

Methods: We examined allergen-specific IL-2 responsiveness induced in lymphocytes in the peripheral blood of infants after infection by RSV. The relationship between the onset of recurrent wheezing and antigen-specific IL-2 responsiveness was analyzed in 25 pediatric patients who could be followed up for 3 years after RSV infection.

Results: Stimulation of lymphocytes with ovalbumin, alpha-casein, and mite (Dermatophagoides farinae) antigens induced significantly higher responsiveness to IL-2 in the RSV-infected infant group than in the healthy infant and disease control groups of the same age. There was no clear correlation between the IgE RAST scores for D. farinae, ovalbumin, and alpha-casein and IL-2 responsiveness. The families of RSV-infected infants had a high incidence of history of allergy (67%), but there was no significant difference in the incidence of patients with positive test results for IL-2 responsiveness between the groups with and without a familial history of allergy. The D. farinae-specific IL-2 responsiveness was significantly increased in the group with the symptom (16 patients) for a value of 1.64 +/- 0.13 (mean +/- SEM) compared with the value of 1.31 +/- 0.21 in the asymptomatic group (9 patients). The incidence of patients with positive test results for IL-2 responsiveness was 68.8% in the symptomatic group and 44.4% in the asymptomatic group. Similarly, the ovalbumin-specific IL-2 responsiveness was significantly increased in the symptomatic group (1.63 +/- 0.17) compared with the asymptomatic group (1.12 +/- 0.26). The incidence of patients with positive test results was 62.5% and 22.2%, respectively. alpha-Casein-specific IL-2 responsiveness was also higher in the symptomatic group than in the asymptomatic group, but the difference was not statistically significant. In the patient groups without RSV infection, on the other hand, the D. farinae-, ovalbumin-, and alpha-casein-specific IL-2 responsiveness in the symptomatic group were all similar to that in the asymptomatic group; no significant increases were detected.

Conclusion: The results indicated that after RSV infection, lymphocytes acquire specific susceptibility to D. farinae, a mite antigen, and food antigens, particularly ovalbumin. Hence, it is thought that positive IL-2 responsiveness specific for D. farinae and/or ovalbumin, detected several months after RSV infection, can be a prediction factor for the onset of allergic diseases, such as recurrent wheezing and bronchial asthma.