Agonists of μ- and δ-opioid receptors in the regulation of IL-2, IL-4, and IFN-γ production by peripheral blood cells in vitro
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It was found that β endorphin stimulates the phytohemagglutinin (PHA)-induced production of interleukin-4 (IL-4) and has no effect on the production of interferon-γ in unfractionated leukocyte suspension. In the culture of purified CD4+ T cells, β-endorphin does not affect the concentration of IL-2, IL-4, and IFN-γ but stimulates the production of IL-4 and inhibits the production of IFN-γ when monocytes are added to the culture. Selective δ-agonist DADLE enhances the PHA-induced production of IL-4-in unfractionated leukocyte suspension and in the system containing CD4+ lymphocytes and monocytes. The synthesis of IFN-γ by purified CD4+ lymphocytes is not changed in the presence of DADLE, DAGO, and Deltorphin II; however, when monocytes are added to the culture, the synthesis rate decreases. β-Endorphin and selective μ-agonist DAGO enhance the production of IFN-γ by stimulated neutrophils. The production of IFN-γ by CD8+ lymphocytes is not affected by β-endorphin. Thus, opioid peptides have predominantly a Th2-polarizing effect, which is monocyte-mediated, hindering the development of cell response by inhibiting IFN-γ and stimulating the production of IL-4 by activating δ-receptor. Neutrophils can also enhance the production of IFN-γ by stimulating μ-receptor.
Keywordsβ-endorphin IL-2 IL-4 interferon-γ opioid receptors lymphocytes
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