Morphine potentiates transforming growth factor-beta release from human peripheral blood mononuclear cell cultures

Opiates modulate a variety of immune responses by peripheral blood mononuclear cells (PBMC). In the present study, we investigated the effect of morphine on the release of several cytokines upon stimulation with mitogens. An interleukin (IL)-4-dependent HT-2 cell proliferation assay was used to quantify transforming growth factor-beta (TGF-beta). IL-6 and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assays. Morphine (1 pM and 10 nM) alone did not significantly modulate the release of TGF-beta, IL-6 or TNF-alpha. Upon stimulation with lipopolysaccharide and phytohemagglutinin, PBMC released more (P less than .01) TGF-beta, IL-6 and TNF-alpha than unstimulated PBMC. Exposure of PBMC to morphine (1 pM) for 24 hr substantially amplified (P less than .05) the release of TGF-beta in the following 24 hr incubation period. Morphine did not alter the release of immunodetectable IL-6 or TNF-alpha from stimulated cells. The amplifying effect of morphine on the release of TGF-beta was mediated through a naloxone-sensitive mechanism. Given the fact that TGF-beta has a potent immunosuppressive effect, morphine-potentiated release of TGF-beta from PBMC may be involved in the immunomodulatory activity ascribed to morphine.