GLUCOCORTICOIDS INHIBIT HUMAN ANTIGEN-SPECIFIC AND ENHANCE TOTAL IGE AND IGG4 PRODUCTION DUE TO DIFFERENTIAL-EFFECTS ON T-CELL AND B-CELL IN-VITRO

Although anti-inflammatory properties of glucocorticoids (GC) are well documented, their activity in allergic diseases is still controversia l. Recently, it has been reported that GC can increase, both in vivo a nd in vitro, the polyclonal production of total IgE. In this study we investigated the effects of GC on the antigen (Ag)-specific IgE respon se in a human in vitro system with peripheral blood mononuclear cells or B cells of bee venom-sensitized individuals that allows the product ion of bee venom phospholipase A(2) (PLA)-specific IgE and IgG4 antibo dies (Ab). PLA-specific Ab were induced by simultaneously activating T cells and B cells specifically with allergen and polyclonally with an ti-CD2 and soluble CD40 ligand (sCD40L) in the presence of interleukin (IL)-4. Indeed, dexamethasone and prednisolone enhanced the formation of total IgE and IgG4 in PBMC, while the production of PLA-specific I gE and IgG4 Ab was selectively inhibited in a dose-dependent manner. T he suppressive effect of GC was mediated during Ag-specific stimulatio n and T cell-B cell interaction. This was due to GC suppressing specif ic T cell proliferation and cytokine production, whereas neither aller gen-specific nor total IgE and IgG4 production by sCD40L/IL-4-stimulat ed pure B cells was affected. In contrast to GC, cyclosporine A inhibi ted both total and PLA-specific IgE and IgG4 secretion in peripheral b lood mononuclear cells and B cell cultures. Further experiments showed that increase in nonspecific total isotype response resulted from inh ibition of IL-4 uptake by cells other than B cells and sufficient avai lability of IL-4 to B cells for isotype switch and synthesis. Furtherm ore, demonstration of opposite regulatory effects of GC on specific an d total isotype formation in vitro, including the inhibition of allerg y-relevant Ag-specific IgE response, may contribute to a better unders tanding of apparently controversial observations, and explain why most allergic patients benefit from GC therapy.