Dynamics in cytokine responses during the development of occupational sensitization to rats

BACKGROUND: Occupational allergy forms an attractive model to study the development of allergic responses, as in some occupations it has a high incidence and develops quickly. In a cohort of starting laboratory animal workers, we previously found 20% sensitization to animal allergens within 2 years. METHODS: We compared cellular responses of incident laboratory animal workers who developed rat-specific sensitization (cases, n = 18) during 2 years of follow-up to control animal workers matched for atopic status but without sensitization after follow-up (controls, n = 18). Practically, this is a case-control study, nested within the cohort. Rat-specific IgE antibodies were measured in sera, and allergen-specific and nonspecific cytokine responses were measured in whole blood and in isolated peripheral blood mononuclear cells. RESULTS: Self-reported allergic symptoms were related to the presence of rat-specific IgE (P ≤ 0.01). Cases developed a rat allergen-specific interleukin (IL)-4 response during sensitization, while controls did not show an increased IL-4 response (at visit D: 33 vs 5 IL-4 producing cells/10(6) cells, P < 0.001). The IL-4 response was related to the levels of rat-specific IgE in cases (visit D: rho = 0.706, P < 0.001). By contrast, allergen-specific IL-10 and interferon γ (IFNγ) responses as well as nonspecific cytokine responses were comparable between cases and controls. CONCLUSION: This study is the first to show the development of an allergen-specific IL-4 response in adult human subjects during allergen-specific sensitization. This IL-4 response was quantitatively associated with the development of the specific IgE antibodies. Allergen-specific or nonspecific IL-10 and IFNγ responses showed no protective effect on the development of allergic sensitization.