Effect of H1-receptor antagonists on proliferative response, cytokine production, and cellular migration of human T cells and macrophages

Cytokine imbalance and cellular migration to inflammatory sites are critical components of allergic diseases. Redirecting cytokine imbalance and inhibiting cell migration therefore represent important therapeutic strategies for the treatment of these disorders. We studied the in vitro effect of the non-sedating H₁-receptor antagonists ebastine, carebastine, epinastine, cetirizine, and ketotifen on cytokine secretion by human T cells under various co-stimulatory conditions and the migratory activity of activated T cells as well as production of pro-inflammatory cytokines by macrophages. Ebastine and carebastine inhibited T cell proliferation and production of IL-4, IL-5, IL-6, and TNF-α by T cells under co-stimulation with CD28 plus CD3, CD26 plus CD3, and CD3 plus phorbol myristate acetate, whereas these drugs had no effect on the production of IL-2 and IFN-γ. Ebastine and carebastine also inhibited T cell migration and production of TNF-α and IL-6 by macrophages. Epinastine inhibited T cell proliferation and production of IL-2, IFN-γ, IL-4, and IL-5, whereas it elicited no effect on the production of IL-6 and TNF-α by T cells and macrophages as well as T cell migration. Cetirizine and ketotifen had no effects on cytokine production and T cell migration. Our results suggest that certain H₁-receptor antagonists, most notably ebastine and carebastine, can influence T cell migration and cytokine production in addition to antagonizing the H₁ receptor. These drugs therefore might be useful against T cell-mediated allergic inflammatory disorders such as asthma, atopic dermatitis, and psoriasis.