Selective Lymphocyte Activation and Inhibition of In Vitro Tumor Cell Growth by Novel Morphinans

Opioids can suppress immune functions and increase susceptibility to developing cancer and infectious diseases. Recently, novel opioid compounds have been synthesized that lack immunosuppressive effects. We evaluated the effects of morphinans with substituted pyrimidine (methyl, phenyl, hydroxy, and amino groups) and pyrazole groups on in vitro rat thymic lymphocyte and splenic macrophage functions, and tumor cell growth. We observed that morphinans with methyl, phenyl, hydroxy, amino, and pyrazole groups at concentrations from 10^-10M to 10^-5M plus Con A (2.5 mg/ml) significantly (P < 0.01) induced 2- to 2.9-, 2.3- to 6.4-, 2.4- to 3.4-, 2.6- to 3.4-, and 2.6- to 3.2- fold increases respectively in thymic lymphoproliferation compared with Con A alone; this effect was reversed by naloxone. Macrophage nitric oxide production was not altered by morphinans. In addition, we observed that all tested morphinans were associated with significant (P < 0.01) in vitro tumor cell growth inhibition of J774A (18-41%), L929 (12-36%), L5178 (9-15%) cell lines in a dose-dependent manner, at doses ranging from 10^-11M to 10^-5M. Morphinans may be applied in clinical situations where immunosuppression is undesirable.