ALLERGEN-INDUCED CYTOKINE PRODUCTION IN ATOPIC DISEASE AND ITS RELATIONSHIP TO DISEASE SEVERITY

The Th2 cytokines, interleukin (IL)-4 and IL-5, have an important role in atopic disease. CD30 is a transmembrane molecule that may be expre ssed on a proportion of activated T-lymphocytes and has been reported to be a marker for Th2 phenotype. Our objective was to compare the in vitro cytokine responses and CD30 expression of peripheral blood monon uclear cells (PBMCs) to stimulation with house dust mite antigen (Derm atophagoides pteronyssinus) in atopic asthmatics, atopic nonasthmatics , and normal subjects, and to see if atopic asthmatic cytokine product ion correlated with symptomatic disease activity and whether cytokine production was allergen-specific. Eighteen atopic asthmatics (all were allocated a symptomatic disease score), 6 atopic nonasthmatics, and 7 healthy nonatopic individuals were studied. Resting serum IL-4 levels were measured, then PBMCs were separated using Lymphoprep density cen trifugation and cultured in modified RPMI 1640 medium. PBMCs were stim ulated with IL-2 alone or with D. pteronyssinus (1,000 subcutaneous un its/ml) with IL-2 and harvested after 5 and IO d. Using monoclonal ant ibodies and flow cytometry we obtained the percentage of CD4(+) T cell s expressing CD30 and the intensity of CD30 staining, Culture supernat ants were analyzed for IL-4 and interferon gamma (IFN-gamma) using an enzyme-linked immunosorbent assay. In 9 atopic asthmatics PBMCs were a lso stimulated nonspecifically using phytohemagglutinin (PHA). IL-4 wa s detectable in the serum of atopic subjects but not in normal subject s, Stimulation of PBMCs with D. pteronyssinus produced significant amo unts of IL-4 in atopic asthmatics and atopic nonasthmatics, but minima l quantities in normal subjects. Much lower levels of IFN-gamma were p roduced by atopic asthmatics in response to D. pteronyssinus compared to atopic nonasthmatics. IFN-gamma levels had an inverse correlation w ith asthmatic symptom score. CD4(+) T-cell expression of CD30 also cor related inversely with IFN-gamma production and IFN-gamma:IL-4 ratio. PHA produced minimal levels of IL-4 compared to specific allergen stim ulation. It is concluded that different groups of atopic patients exhi bit different patterns of allergen-induced cytokine production. In vit ro allergen-induced cytokine production in atopic asthmatics correlate d with symptomatic disease activity, and is allergen-specific.