Hev b 6.01 and Hev b 5 induce pro‐inflammatory cytokines and chemokines from peripheral blood mononuclear cells in latex allergy

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Abstract
Summary: Background Hev b 6.01 (prohevein) and Hev b 5 [acidic natural rubber latex (NRL) protein] are major IgE‐binding allergens in NRL allergy.Objective To examine allergen‐specific cytokine and chemokine responses in NRL‐allergic patients.Methods Fourteen NRL‐allergic patients and 10 healthy controls participated in the study. Hev b 6.01 and Hev b 5 were purified under non‐denaturating conditions by chromatographic methods. Specific IgE antibodies were measured by ELISA and proliferation of peripheral blood mononuclear cells (PBMC) by 3H‐thymidine incorporation assay. Allergen‐specific induction of cytokine and chemokine mRNA in PBMC was measured by real‐time PCR and protein levels by ELISA. Surface expression of chemokine receptors was analysed by flow cytometry.Results Twelve (86%) NRL‐allergic patients had positive skin prick test reactions and IgE antibodies against Hev b 6.01, but less than 30% responded to Hev b 5. Cell proliferation against Hev b 6.01, but not against Hev b 5, was significantly increased. Both allergens elicited significantly higher expression of pro‐inflammatory and T‐helper type 2 cytokines (TNF, IL‐12p40, IL‐13) and chemokines (CCL3, CCL4, CCL20) in the NRL‐allergic patients than in controls. Interestingly, mRNA expression of the regulatory cytokine TGF‐β1 was reduced, whereas IL‐10 expression was enhanced after allergen stimulations in patients with NRL allergy. Finally, the NRL‐allergic patients showed increased CCR4 expression on CD3+CD8− T cells and decreased CXCR3 expression on CD3+CD8+ T cells.Conclusion Allergen‐specific induction of cytokines and chemokines in PBMC and chemokine receptor expression on circulating T cells may contribute to the pathogenesis of NRL allergy.

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