[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].

It was found that ß-endorphin stimulates the PHA (phytohemagglutinin)-induced production of interleukin-4 and has no affect on the production of interferon-gamma in unfractionated leukocytic suspension. In the culture of purified CD4+ T cells, ß-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 adding monocytes to the culture. Selective δ-agonist DADLE enhances the PHA-induced production of IL-4 in unfractionated leukocytic suspension and in CD4+ lymphocytes+monocytes system. The synthesis of IFN-γ by purified CD4+ lymphocytes is not afected by the presence of DADLE, DAGO ad Deltorphin II; but when adding monocytes to the culture, the synthesis rate decreases. ß-endorphin and selective µ-agonist DAGO enhance the production of IFN-γ by stimulated neutrophils. The production of IFN-γ in CD8+ lymphocytes is not affected by ß-endorphin. Thus, opioid peptides have a predominantly Th2 polarizing effect, which is monocyte-mediated, hindering the development of cell response by inhibiting IFN-γ, and stimulating the production of I L-4 by activating δ-receptor. On the other hand, neutrophils can enhance the production of IFN-γ by stimulating µ-receptor.

ß-Endorphin effects on antibody production, proliferation, and secretion of Th1/Th2 cytokines in vivo.

Intraperitoneal injection of ß-endorphin in doses of 1, 0.01, and 0.0005 µg/kg under conditions of systemic immunization increased the count of antibody-producing cells in the spleen and the titer of anti-erythrocyte antibodies in the plasma of experimental animals. Intraperitoneal ß-endorphin stimulated proliferative activity of splenocytes in mice in the presence of both B- and T-cell mitogen, did not change the production of IFN-γ, reduced the level of IL-2, and stimulated the secretion of IL-4, the main Th2-polarizing factor.

Regulation of interleukin-1beta and interleukin-8 production by agonists of mu and delta opiate receptors in vitro.

The studies reported here showed that beta-endorphin at concentrations of 10(-7)-10(-11) M increased interleukin-1beta (IL-1beta) production in unfractionated leukocyte suspensions both in the presence of 0.1 microg/ml lipopolysaccharide (LPS) and in cultures not stimulated with LPS. Interleukin-8 (IL-8) production by leukocytes was inhibited by beta-endorphin at concentrations of 10(-7) and 10(-11) M in the presence of LPS. The stimulatory effect of beta-endorphin on IL-1beta production was not blocked by naloxone or naltrindole. Suppression of IL-8 production was blocked by naloxone and naltrindole. In the mononuclear cell and neutrophil fractions, beta-endorphin and the delta agonist DADLE increased IL-1beta synthesis in both the spontaneous and stimulated versions of the test, while beta-endorphin and the delta agonist DADLE inhibited IL-8 production in the mononuclear cell and neutrophil fractions only in LPS-stimulated cultures. The mu agonist DAGO had no effect on IL-1beta production by mononuclear cells or neutrophils, though it suppressed LPS-induced secretion of IL-8 by neutrophils.

Role of beta-endorphin in the regulation of proinflammatory cytokine production by peripheral blood monocytes in vitro.

beta-Endorphin activated interleukin-1beta production in the culture of unfractionated cells with lipopolysaccharide, but had no effect on the synthesis of tumor necrosis factor-alpha and interleukin-6. This peptide produced a slight stimulatory effect on spontaneous production of interleukin-1beta by cultured leukocytes. Opioid receptor blockade with naloxone and naltrindole did not abolish the stimulatory effect of beta-endorphin on interleukin-1beta production. beta-Endorphin did not modulate the synthesis of interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 in a purified fraction of monocytes.

The effects of rotation stress on measures of immunity. The role of opiate receptors.

Experiments were performed on mongrel male rats to study the effects of blockade of delta, mu, and kappa opiate receptors on antibody formation, delayed-type hypersensitivity (DTH), and changes in the numbers of antibody-forming cells (AFC) and nucleated cells in the lymph nodes and spleen in a local form of immune response in a model of rotation stress. These studies showed that rotation stress led to mild suppression of immune inflammation in DTH, significant increases in the numbers of AFC and nucleated cells in regional lymph nodes, but no change in the peripheral blood antibody titer. Blockade of delta, mu, and kappa opiate receptors with naloxone altered these stress-induced effects. It is suggested that abolition of the stimulating effect of rotation stress on the number of AFC and depression of DTH may be associated with blockade of the effects of beta-endorphin and met-enkephalin, which act predominantly via stimulation of delta receptors.