Differential modulation of human immunoglobulin isotype production by the neuropeptides substance P, NKA and NKB

The modifying effects of tachykinins substance P, neurokinin A and neurokinin B on immunoglobulin production were analyzed in an in vitro culture system. Purified human T- and B-cells were stimulated with TGF(beta 2) and IL-5 to induce preferential IgA production. Neuropeptides had the following effects. (1) The levels of IgA and IgG(4) production were enhanced by IL-5 and TGF(beta 2); IgA levels remained constant or were slightly augmented by neuropeptides, whereas IgG(4) was further augmented. (2) IL-5 and TGF(beta 2) did not alter IgG(3) production, but neuropeptides stimulated secretion of this subclass. (3) IgG(1) and IgM production were inhibited by IL-5 and TGF(beta 2). This effect was prevented by neuropeptides. (4) Other isotypes including IgG(2) and IgE remained unaffected. Except for IgM, these effects were blocked by specific receptor antagonists indicating specificity. The tachykinin receptor NK-1 mRNA was detected in B- and T-cells, whereas NK-3 mRNA was only present in T- and B-cell coculture following activation. Furthermore, neuropeptide effects depended on cytokine co-stimulation and the presence of T-cells. These results suggest that neuropeptides are potent modifiers of preferential IgA synthesis. (C) 1999 Elsevier Science B.V. All rights reserved.