Proliferation, interleukin-2 production and receptor expression in peripheral blood mononuclear cells from colorectal...

Peripheral blood mononuclear cells (PBMC) were cultured with phytohemagglutinin (PHA) in 46 colorectal cancer patients and 27 normal controls. By collectively comparing the cancer patients with the normal controls, the cancer patients had: (1) decreased interleukin-2 (IL-2) secretion, (2) fewer interleukin-2 receptor (IL-2R) expression on cell surface, and (3) less 3H thymidine incorporation. The ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), and the calcium ionophore, A23187, in co-stimulation with PHA, to enhance the IL-2 secretion, IL-2R expression and 3H thymidine incorporation were studied in the PBMC of colorectal cancer patients. By adding A23187 into the PHA-stimulated PBMC from colorectal cancer patients, IL-2 production and IL-2R expression were increased up to levels equal to that obtained in PHA-stimulated PBMC from normal controls. Whereas there was no significant increase in proliferative response. However, PMA has no effect on all three parameters. A23187 is known to be effective in elevating cytosolic free Ca2+ and PMA is regarded as an activator of protein kinase C. Therefore, we may conclude that the impairment of IL-2 production and IL-2R expression in PHA-stimulated cultures is mainly due to failure of the free Ca2+ release which can be repaired by A23187. While protein kinase C activation may not be impaired since its deficit in IL-2 production and IL-2R expression can not be corrected by PMA.