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 vasoactive intestinal peptide (VIP) for 1 to 3 days only modestly suppressed or enhanced the production of IgA and IgM, but not IgG. The effects of twice daily additions of 10(-12) to 10(-7) mol/L VIP for up to 18 days on pokeweed mitogen-stimulated peripheral blood mononuclear cells (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 97%; 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. Suppression of IgM production by 10(-9) mol/L VIP was significant and was observed first on day 5 and persisted through day 14. VIP did not alter IgA production or affect the proliferation or viability of PBMCs. The production of IgE by interleukin-4 stimulated PBMCs was enhanced consistently in two subjects but not in two other subjects. The duration of exposure to nanomolar concentrations of VIP is thus a critical determinant 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.
Hassner
A
A
Department of Medicine, University of California, Medical Center, San Francisco 94143-0724.
Lau
M S
MS
Goetzl
E J
EJ
Adelman
D C
DC
D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D015847:Interleukin-4; D014660:Vasoactive Intestinal Peptide; D007073:Immunoglobulin E