title: Effect of vasoactive intestinal peptide, somatostatin, and substance P on spontaneous IgE and IgG4 production in atopic patients.
abstract: The effect of vasoactive intestinal peptide (VIP), somatostatin (SOM), and substance P (SP) on spontaneous human IgE and IgG4 production in atopic patients was studied. In cultures of mononuclear cells (MNC), VIP inhibited both IgE and IgG4 production without affecting IgM, IgA, IgG1, IgG2, or IgG3 production. In contrast, SOM inhibited only IgE production whereas SP inhibited only IgG4 production without affecting production of other isotypes or other IgG subclasses. The effect of neuropeptides was specific because each was specifically blocked by a corresponding 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 inhibition of IgE and IgG4 production by neuropeptides could not have been mediated by IFN-alpha, IFN-gamma, or PGE2 because the addition of anti-IFN-alpha, anti-IFN-gamma, and indomethacin, respectively, did not reverse the inhibition. In contrast to their effects on MNC, neuropeptides did not affect production of either IgE or IgG4 by purified B cells; the addition of either T cells or monocytes to B cells had no effect on this. However, neuropeptides were effective in inhibiting IgE and IgG4 production by B cells cultured together with both T cells and monocytes. Depletion of sIgE+ and sIgG4+ B cells resulted in abrogation of IgE and IgG4 production, respectively. However, stimulation of sIgE- B cells with IL-4 plus anti-CD 40 mAb induced IgE production, which was inhibited by VIP and SOM, but not SP, in the presence of both T cells and monocytes. These results suggest that neuropeptides inhibited spontaneous IgE and IgG4 production by interaction with sIgE+ and sIgG4+ B cells in a T cell- and monocyte-dependent fashion. In addition, VIP and SOM also inhibited IgE production by modulating switching induced by IL-4 plus anti-CD 40 mAb in a T cell- and monocyte-dependent fashion.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kyoto University Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kimata
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: H
authors.initials: H
authors.lastname: Mikawa
mesh_terms: D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008212:Lymphocyte Depletion; D009000:Monocytes / Q000502:physiology; D017455:Receptors, IgE / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D007074:Immunoglobulin G; D017455:Receptors, IgE; D017452:Receptors, IgG; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D007073:Immunoglobulin E; D013004:Somatostatin