MORPHINE INHIBITS THE RELEASE OF TUMOR-NECROSIS-FACTOR IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR CELL-CULTURES

Opiates modulate a variety of immune responses of peripheral blood mononuclear cells (PBMC). When PBMC were treated with morphine for 24 h, cells released less (P<0.05) bioactive TNF, a cytokine important in host defense, in the following 24-h incubation period when stimulated with lipopolysaccharide and phytohemagglutinin. Morphine alone did not significantly alter the release of TNF from PBMC cultures. Pretreatment of PBMC cultures for 1 h with naloxone blocked (P<0.05) the inhibitory effect of morphine on the release of TNF upon stimulation with phytohemagglutinin, but not with lipopolysaccharide, suggesting the involvement of an opioid receptor. The mechanism of morphine-induced suppression of TNF release appears to be counteracted by the effect of this opiate on the release of transforming growth factor (TGF)-beta, since antibodies to this immunoregulatory cytokine further enhanced morphine-related inhibition of TNF release. Taken together, these findings indicate that morphine suppresses the release of bioactive TNF from PBMC and that TGF-beta plays a modulatory role in this inhibitory process.