Selective Lymphocyte Activation and Inhibition of In Vitro Tumor Cell Growth by Novel Morphinans
Ricardo Gomez-Flores, Kimberly R. Vietti, William J. Dunn, Reyes Tamez-Guerra and Richard J. Weber
DOI : 10.3844/ajisp.2006.1.7
American Journal of Immunology
Volume 2, 2006
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.
© 2006 Ricardo Gomez-Flores, Kimberly R. Vietti, William J. Dunn, Reyes Tamez-Guerra and Richard J. Weber. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.