Suppression of cytokine response by anti-allergic drugs

Abstract

Rationale To date, the primary pharmacological target of antiallergic drugs (antihistamines) has been regarded as the histamine H 1-receptor. However, previous studies have shown that terfenadine may suppress IL-4–modulated gene expression of T-cell cytokines, indicating that this agent may have immunomodulatory properties. Therefore, in the present study we assessed whether other currently available antihistamines also possess immunomodulatory properties. Methods T-cells were isolated from peripheral blood samples, pre-incubated with various doses of Cetirizine, Loratadine, Olopatadine or Fexofenadine for 30 minutes and then stimulated with interleukin (IL)-12 or IL-4 to skew the immune response towards Th1 or Th2. Six hours later RNA was extracted and semi-quantitative RT-PCR was performed using primers for IL-4, IL-5 or interferon (IFN)-γ. Supernatants were collected 24 hours after stimulation and ELISA assays were performed to determine the production of cytokines. Results RT-PCR revealed that IL-12–induced expression of IFN-γ was partially suppressed by Loratadine or Fexofenadine, while all agents markedly inhibited IL-4–induced expression of IL-4 and IL-5. ELISA assays demonstrated that IL-12–induced IFN-γ production was moderately, but significantly suppressed by Cetirizine or Fexofenadine ( p<0.05). Furthermore, all agents, except Cetirizine, downregulated IL-4–induced IL-5 production from T-cells. Conclusions Our study demonstrates that antihistamines may exert modulatory effects on IL-4– or IL-12–induced T-cell activation. Since the local cytokine milieu of allergic disease may be biased to Th1 or Th2, depending on the disease state or conditions, these findings may provide a further understanding of the impact of antihistamines in allergic conditions.