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Neuropeptides are potent modulators of human in vitro immunoglobulin E synthesis
I Aebischer1, M R Stämpfli, A Zürcher
1Institute of Clinical Immunology, University of Bern, Switzerland.
Insights
Adrenocorticotropin hormone (ACTH) influences immunoglobulin E (IgE) synthesis by modulating accessory cells, not directly affecting B or T cells. This suggests ACTH and related peptides play a role in regulating IgE production.
Area of Science:
- Immunology
- Endocrinology
Background:
- Immunoglobulin E (IgE) synthesis is a complex process regulated by various factors.
- Adrenocorticotropin hormone (ACTH) is primarily known for its role in the stress response and steroidogenesis.
Purpose of the Study:
- To investigate the effect of ACTH on the regulation of IgE synthesis.
- To elucidate the cellular mechanisms by which ACTH influences IgE production.
Main Methods:
- Peripheral blood mononuclear cells were cultured and stimulated with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody to induce IgE synthesis.
- ACTH and related peptides were added to assess their impact on IgE, IgG, and IgM synthesis.
- Experiments involved purified B cells, T cells, and CD14-positive monocytes to determine the cellular mediators of ACTH's effect.
Main Results:
- ACTH demonstrated dose-dependent enhancement or inhibition of IgE synthesis.
- ACTH and related peptides (CRF, alpha-MSH) affected IgE synthesis but not IgG or IgM.
- The effects of ACTH were mediated by accessory cells, specifically CD14-positive monocytes, and not by direct action on B or T cells.
Conclusions:
- ACTH and related peptides modulate the microenvironment, influencing IgE class switching.
- Accessory cells are crucial mediators of ACTH's effect on IgE synthesis.
- These findings highlight a novel role for ACTH in immune regulation, particularly in IgE production.
Abstract:
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.