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 mon onuclear cells (PBMC). When PBMC were treated with morphine for 24 h, cells released less (P<0.05) bioactive TNF, a cytokine important in ho st defense, in the following 24-h incubation period when stimulated wi th lipopolysaccharide and phytohemagglutinin. Morphine alone did not s ignificantly alter the release of TNF from PBMC cultures. Pretreatment of PBMC cultures for 1 h with naloxone blocked (P<0.05) the inhibitor y effect of morphine on the release of TNF upon stimulation with phyto hemagglutinin, but not with lipopolysaccharide, suggesting the involve ment of an opioid receptor. The mechanism of morphine-induced suppress ion of TNF release appears to be counteracted by the effect of this op iate on the release of transforming growth factor (TGF)-beta, since an tibodies to this immunoregulatory cytokine further enhanced morphine-r elated inhibition of TNF release. Taken together, these findings indic ate that morphine suppresses the release of bioactive TNF from PBMC an d that TGF-beta plays a modulatory role in this inhibitory process.