Effects of hydrocortisone on the differentiation of human T helper 2 cells.

We investigated the effects of the neuroendocrine modulator hydrocortisone (HC) on Th2 differentiation of human naive CD4+ T cells with and without CD28 co-stimulation. Human naive CD4+ T cells were isolated and purified from umbilical cord blood mononuclear cells from full-term newborn infants. CD4+ T cells were treated with different concentrations of HC under Th0 or Th2 culture conditions. Th0 conditions included stimulation by immobilized monoclonal antibodies (mAbs) against CD3 and CD28; Th2 conditions were the same + rhIL-4. Parallel cultures excluded the CD28 mAb. Th1 (IL-2, INF-γ)- and Th2 (IL-4, IL-5)-type cytokines were quantified in culture supernatants by ELISA and within cells by flow cytometry. For both Th0 and Th2 culture conditions, HC significantly inhibited Th1 cytokines' release (IL-2 and INF-γ). For Th0 culture conditions, HC slightly increased IL-4 expression (Th2 cytokine). However, for Th2 culture conditions, HC inhibited the IL4-induced production of IL-4. Although the absolute cytokine amounts were decreased, absence of CD28 co-stimulation did not alter these 'trends'. Our findings indicate that HC can alter the Th1/Th2 balance by inhibiting the production of Th1-type cytokines. HC can also diminish the extensive Th2 differentiation induced by IL-4.