LYMPHOBLASTOID INTERFERON-ALPHA INHIBITS T-CELL PROLIFERATION AND EXPRESSION OF EOSINOPHIL-ACTIVATING CYTOKINES

T cell-derived cytokines, such as interleukin-5 (IL-5) and granulocyte -macrophage colony-stimulating factor (GM-CSF) activate eosinophils, w hereas other cytokines, such as tumor necrosis factor (TNF)-alpha and IL-13, determine eosinophil recruitment, Interferon-alpha (IFN-alpha), a leukocyte-derived cytokine, has been shown to have beneficial effec ts in eosinophil-mediated disorders, such as the hypereosinophilic syn drome and a murine model of allergic asthma, where it inhibited eosino phil recruitment, We tested the hypothesis that IFN-alpha acted in eos inophil-mediated disorders by modulating T cell cytokine expression, P eripheral blood mononuclear cells (PBMC) or human ragweed-specific T-H 1 (2B8) and T-H2 (2D2) T cell clones were cultured in the presence of 5 mu g/ml of phytohemagglutinin (PHA) or 25 mu g/ml of antigen Amb a 1 (short ragweed allergen), respectively, and lymphoblastoid IFN-alpha (varying from 0 to 10,000 U/ml), We assessed T cell proliferation by [ H-3]thymidine incorporation and production of IL-5 and GM-CSF by ELISA , Expression of cytokine transcripts was analyzed by the reverse trans cription-polymerase chain reaction technique (RT-PCR), IFN-alpha induc ed a dose-dependent suppression of T cell proliferation of both PBMC ( p < 0.001) and the T cell clones (p < 0.001), IFN-alpha inhibited gene expression of IL-5, GM-CSF, TNF-alpha, and IL-13 in PBMC, Furthermore , IFN-alpha significantly inhibited mitogen-induced and antigen-induce d production of IL-5 and GM-CSF. IFN-alpha may benefit eosinophil-medi ated disorders by inhibiting T cell function and production of cytokin es active on human eosinophils.