Glucocorticoids increase the synthesis of immunoglobulin E by interleukin 4-stimulated human lymphocytes.
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.
Wu
C Y
CY
Research Center, Notre-Dame Hospital, University of Montreal, Quebec, Canada.
Sarfati
M
M
Heusser
C
C
Fournier
S
S
Rubio-Trujillo
M
M
Peleman
R
R
Delespesse
G
G
D015703:Antigens, CD / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000378:metabolism*; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000502:physiology; D014066:Palatine Tonsil / Q000166:cytology; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D003524:Cyclosporins; D011961:Receptors, Fc; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D006854:Hydrocortisone