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.

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.

Beta-endorphin stimulates phytohemagglutinin-induced production of IL-4 and does not modify the production of gamma-IFN in nonfractionated leukocyte suspension. In a culture of purified CD4+ T-cells, beta-endorphin does not modify the levels of IL-4 and gamma-IFN, but stimulates the production of IL-4 and inhibits gamma-IFN production after addition of monocytes to CD4+ lymphocytes. Stimulation of IL-4 synthesis by beta-endorphin is mediated by the cycloxygenase cycle products. Hence, beta-endorphin shifts T-helper polarization towards Th2 cells with subsequent predominance of the humoral form of the immune response.