Glucocorticoids increase the synthesis of immunoglobulin E by interleukin 4-stimulated human lymphocytes
1Research Center, Notre-Dame Hospital, University of Montreal, Quebec, Canada.
Insights
Hydrocortisone (HC) significantly boosts immunoglobulin E (IgE) production in human lymphocytes stimulated by interleukin 4 (IL-4). This glucocorticoid effect enhances B cell differentiation into IgE-producing cells, independent of T cells.
Area of Science:
- Immunology
- Endocrinology
Background:
- Interleukin 4 (IL-4) is a key cytokine in the induction of immunoglobulin E (IgE) synthesis.
- Glucocorticoids, like hydrocortisone (HC), are known to modulate immune responses.
Purpose of the Study:
- To investigate the specific effects of hydrocortisone (HC) on interleukin 4 (IL-4)-induced immunoglobulin E (IgE) synthesis in human lymphocytes.
- To elucidate the mechanisms underlying HC's influence on IgE production, including its interaction with cellular components and other cytokines.
Main Methods:
- Human peripheral blood mononuclear cells (PBMCs) were stimulated with IL-4 in the presence of varying concentrations of HC.
- Effects on IgE synthesis, interferon-gamma (IFN-gamma) production, and the expression of Fc epsilon RII (CD23) were assessed.
- Monocyte and T cell depletion experiments were performed to determine their roles.
Main Results:
- HC markedly increased IL-4-stimulated IgE synthesis in a dose-dependent manner (0.1-10 microM).
- HC's effect was observed in both early (IL-4 dependent) and late (IL-4 independent) phases of the response.
- HC inhibited soluble CD23 production and Fc epsilon RII expression but did not require IFN-gamma inhibition.
- Monocytes were crucial for HC's effect, amplifying cellular interactions; T cells were not required but could further enhance IgE production.
Conclusions:
- Hydrocortisone acts synergistically with IL-4 to promote B cell differentiation into IgE-producing cells.
- The mechanism involves enhanced monocyte-lymphocyte interactions, independent of T cells and IFN-gamma inhibition.
- HC's potentiation of IgE synthesis has significant implications for understanding allergic responses and immune modulation.
Abstract:
This study indicates that hydrocortisone (HC) markedly increases the synthesis of immunoglobulin E (IgE) by interleukin 4 (IL-4)-stimulated human lymphocytes. The effect is glucocorticoid specific and is obtained with low concentrations of HC (0.1-10 microM). In both the early and the late phase of the IL-4-induced response HC exerts its effects which are respectively IL-4 dependent and IL-4 independent. The IgE potentiation cannot be explained by the inhibition of interferon-gamma (IFN-gamma) production since it is observed in the absence of endogenous secretion of IFN-gamma. HC inhibits the production of IgE-binding factors (soluble CD23) and the expression of the low-affinity receptor for IgE, also known as the (Fc epsilon RII) CD23 antigen; however, the residual expression of Fc epsilon RII by IL-4- and HC-treated peripheral blood mononuclear cells (PBMCs) is important since the IgE response of these cells is markedly inhibited by anti-CD23 monoclonal antibody. HC acts mainly by amplifying the cellular interactions between monocytes and lymphocytes; indeed, HC has no effect on monocyte-depleted PBMCs, and moreover, monocytes cannot be replaced by soluble factors. Most importantly, T cells are not required for the induction of IgE synthesis by costimulation with IL-4 and HC. However, the IgE response of rigorously T cell-depleted PBMCs may be further increased by the addition of T cells. Further analysis of the permissive effect of HC on the synthesis of IgE by T cell-depleted PBMCs suggests that HC acts in synergy with IL-4 to trigger the activation and the differentiation of B cells into IgE-producing cells.
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