IL-10 inhibits allergen-specific TH2 cytokine production by human peripheral blood mononuclear cells from patients with ragweed allergies

Abstract

~ A IL-10 Inhibits Allergen-Specific TH2 Cytokine Production by 1 ~jl-lr Human Peripheral Blood Mononuclear Cells From Patients With Ragweed Allergies J Sun, Susanna Goncharova, M Conway, A Dalrymple, Elizabeth C Cates, Martin R Stampfli, B Wong, Susan Waserman, Manel Jordana McMaster University, Hamilton, ON, Canada Type 2 polarized T cells and their effector cytokines play a central role in allergic diseases. The objective of this study was to investigate whether ILl0, a cytokine with powerful immuno-suppressive activities, inhibits Th2 cytokine production by peripheral blood mononuclear cells (PBMC) from patients with ragweed allergies. The patients were assessed by skin prick test and clinical history, and PBMC were isolated from these ragweed allergic individuals and non-atopic controls prior to pollen season. PBMC were stimulated with a ragweed pollen extract and cytokine synthesis was measured in culture supematants. Spontaneous production of IL-5 and IL-13 varied with each individual and was not significantly different between the atopic and non-atopic group. In ragweed allergic patients, addition of ragweed extract to the cell culture markedly enhanced levels of IL-5 and IL-13. In contrast, PBMC from non-atopic controls did not respond to ragweed stimulation. Both spontaneous and allergen-induced IL-5 and IL13 production were significantly inhibited by recombinant human IL10. IL10 also suppressed Th2 cytokine production induced by PMA, a T cell polyclonal stimulator. Interestingly, IL-4 synthesis could not be detected in any of the samples tested. We are currently assessing the impact of IL-10 on chemokine production. We also extracted RNA from cultured cells at 3h, 6h, 12h, 24 h, 72h, and 5 days and are assessing the expression of chemokine receptors and co-stimulatory molecules using real time quantitative PCR. Our findings in samples collected prior to pollen season will be compared to samples being generated during pollen season. In summary, PBMC from ragweed allergic individuals produce significant levels of IL-5 and IL-13 in response to ragweed stimulation. This response is inhibited by exogenous IL-10. Thus, our results further the notion that IL10 has therapeutic potential in allergic diseases.