RETINOIDS INHIBIT IL-4-DEPENDENT IGE AND IGG1 PRODUCTION BY LPS-STIMULATED MURINE SPLENIC B-CELLS

The effects of retinoids (all-trans-retinoic acid (RA) and vitamin A) and hydrocortisone (HC) on the IL-4-dependent IgE and IgG1 response by mouse whole spleen cells and splenic B cells were studied. Whole spleen cells were cultured for 8 days in the presence of LPS and IL-4 and the supernatants were assayed for IgG1 and IgE. The levels of the two classes were enhanced about twofold by the addition of HC at 10 nM. The addition of retinoids to the above culture system within 1 day from the start strongly inhibited both IgG1 and IgE responses. The concentration inhibiting both of the reactions by 50% was about 3-10 nM for RA and 300 nM-1 mu M for vitamin A. In the case of splenic B cells, HC also showed an enhancing effect on the IgG1 and IgE production at extremely low concentrations (20 pM-2 nM), but at higher concentrations (above 10 nM) it was inhibitory, IL-4-dependent IgG1 and IgE production of LPS-stimulated splenic B cells was also inhibited by retinoids. The concentration giving 50% inhibition was 0.2 nM for RA and 150 nM for vitamin A. Exogenous TGF-beta 1 also inhibited the IL-4-dependent IgG1 and IgE production by splenic B cells and the inhibition was reverted in the presence of the specific neutralizing antibody to TGF-beta 1. However, the inhibition by 1 nM RA could not be abolished by the excess antibodies to TGF-beta 1 and TGF-beta 2. (C) 1995 Academic Press, Inc.