Neuropeptides are potent modulators of human in vitro immunoglobulin E synthesis.
We determined the effect of adrenocorticotropin hormone (ACTH) on the regulation of IgE synthesis. Depending on the concentration, ACTH enhanced or inhibited IgE synthesis in a culture system where IgE synthesis was induced with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody in peripheral blood mononuclear cells. Similar effects on IgE synthesis were observed by adding ACTH-related peptides, e.g. corticotropin-releasing factor (CRF), the inducer of ACTH, or alpha-melanocyte stimulating hormone (alpha-MSH), a cleavage product of ACTH. However, ACTH had no effect on IgG or IgM synthesis in this culture system. ACTH did not act directly on either B or T cells as there was no influence on IgE synthesis in a system using purified B cells alone or co-cultured with T cells. The effect of ACTH on IgE synthesis was mediated by accessory cells. This was shown by priming purified CD14-positive monocytes with ACTH and reconstitution experiments. Therefore, these findings suggest that ACTH and the related peptides CRF and alpha-MSH can influence the microenvironment modulating an IL-4 and anti-CD40 monoclonal antibody driven class switching to IgE via accessory cells.
Aebischer
I
I
Institute of Clinical Immunology, University of Bern, Switzerland.
Stämpfli
M R
MR
Zürcher
A
A
Miescher
S
S
Urwyler
A
A
Frey
B
B
Luger
T
T
White
R R
RR
Stadler
B M
BM
D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009479:Neuropeptides / Q000502:physiology*; D014066:Palatine Tonsil / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000521:alpha-MSH / Q000502:physiology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D009479:Neuropeptides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone