Strong epidemiological evidence now links the development of childhood asthma with the persistence of T helper lymphocyte Type 2 (Th2) cytokine immune responses during early infancy. However, the ontogeny of human cytokine immune responses and the environmental factors influencing their development have not been fully elucidated. Several lines of evidence support the hypothesis that RSV infection during early infancy induces and amplifies the persistence of Th2 cytokine immune responses. Moreover, results from recent studies suggest that diminished IL-12 and/or IL-10 production by dendritic cells (DCs) is a mechanism by which this occurs. The long-term goal of the applicant's career is to conduct patient-oriented research to: 1) elucidate the mechanism by which RSV infection predisposes to the persistence of Th2 cytokine immune response during early infancy and the later development of childhood asthma; and 2) identify potential strategies to attenuate or prevent the development of RSV infection and/or childhood asthma.
The specific aims of this proposal are to: 1) characterize the ontogeny of human cytokine immune responses during early infancy; 2) investigate the effect of RSV infection during early infancy on these immune responses; and 3) to develop a model for investigating the relationship between RSV-induced immune responses during early infancy and the later development of childhood asthma. This observational, prospective, cohort study will enroll healthy infants at two weeks of age. Blood will be obtained for immune studies at: 1) two weeks of age; 2) the time of primary RSV infection during early infancy; and 3) one month following primary RSV infection. Data will be analyzed to determine whether RSV infection during early infancy alters the ontogeny of DC IL-12 and IL-10 production and Th2 cytokine responses. In addition to providing insight into the mechanism by which RSV infection may predispose to the development of childhood asthma, this proposal will allow the applicant to gain skills that are necessary to develop into an independent and productive clinical investigator.
| Gentile, Deborah; Howe-Adams, Judith; Trecki, Jordan et al. (2004) Association between environmental tobacco smoke and diminished dendritic cell interleukin 10 production during infancy. Ann Allergy Asthma Immunol 92:433-7 |
| Gentile, Deborah A; Schreiber, Rachel; Howe-Adams, Judith et al. (2004) Diminished dendritic cell interleukin 10 production in atopic children. Ann Allergy Asthma Immunol 92:538-44 |
