EFFECT OF VASOACTIVE-INTESTINAL-PEPTIDE, SOMATOSTATIN, AND SUBSTANCE-P ON SPONTANEOUS IGE AND IGG4 PRODUCTION IN ATOPIC PATIENTS

The effect of vasoactive intestinal peptide (VIP), somatostatin (SOM), and substance P(SP) on spontaneous human IgE and IgG4 production in a topic patients was studied. In cultures of mononuclear cells (MNC), VI P inhibited both IgE and IgG4 production without affecting IgM, IgA, I gG1, IgG2, or IgG3 production. In contrast, SOM inhibited only IgE pro duction whereas SP inhibited only IgG4 production without affecting pr oduction of other isotypes or other IgG subclasses. The effect of neur opeptides was specific because each was specifically blocked by a corr esponding neuropeptide antagonist. To achieve the effect noted above, neuropeptides must be added at the start of the culture. IFN-alpha and IFN-gamma were found to inhibit both IgE and IgG4 production whereas prostaglandin E2 (PGE2) inhibited only IgE production. However, the in hibition of IgE and IgG4 production by neuropeptides could not have be en mediated by IFN-alpha, IFN-gamma, or PGE2 because the addition of a nti-IFN-alpha, anti-IFN-gamma, and indomethacin, respectively, did not reverse the inhibition. In contrast to their effects on MNC, neuropep tides did not affect production of either IgE or IgG4 by purified B ce lls; the addition of either T cells or monocytes to B cells had no eff ect on this. However, neuropeptides were effective in inhibiting IgE a nd IgG4 production by B cells cultured together with both T cells and monocytes. Depletion of sIgE+ and sIgG4+ B cells resulted in abrogatio n of IgE and IgG4 production, respectively. However, stimulation of sI gE- B cells with IL-4 plus anti-CD 40 mAb induced IgE production, whic h was inhibited by VIP and SOM, but not SP, in the presence of both T cells and monocytes. These results suggest that neuropeptides inhibite d spontaneous IgE and IgG4 production by interaction with sIgE+ and sI gG4+ B cells in a T cell- and monocyte-dependent fashion. In addition, VIP and SOM also inhibited IgE production by modulating switching ind uced by IL-4 plus anti-CD 40 mAb in a T cell- and monocyte-dependent f ashion.