ISOTYPE-SPECIFIC REGULATION OF HUMAN LYMPHOCYTE-PRODUCTION OF IMMUNOGLOBULINS BY SUSTAINED EXPOSURE TO VASOACTIVE-INTESTINAL-PEPTIDE

Exposure of lymphocytes to nanomolar to micromolar concentrations of v asoactive intestinal peptide (VIP) for 1 to 3 days only modestly suppr essed or enhanced the production of IgA and IgM, bw not IgG. The effec ts of twice daily additions of 10(-12) to 10(-7) mol/L VIP for up to 1 8 days on pokeweed mitogen- stimulated peripheral blood mononuclear ce lls (PBMCs) from normal human subjects was examined by quantifying the production of IgG, IgM, and IgA. The maximum suppression of IgG by 10 (-9) mol/L VIP was 79% +/- 33% (mean +/- SD) (range, 41% to 970%; p < 0.015) on day 9 and 84% +/- 1% (range, 74% to 96%; p < 0.0001) on day 14 and was significant at 6 x 10(-10) to 4 x 10(-9) mol/L VIP. Suppres sion of IgM production by 10(-9) mol/L VIP was significant and was obs erved first on day 5 and persisted through day 14. VIP did not alter I gA production or affect the proliferation or viability of PBMCs. The p roduction of IgE by interleukin-4 stimulated PBMCs was enhanced consis tently in two subjects but not in two other subjects. The duration of exposure to nanomolar concentrations VIP is thus a critical determinan t of its immunoregulatory effect, as manifested by late suppression of production of IgG and IgM and concurrent enhancement of production of IgE in some subjects.