Inhibition of spleen cell cytotoxic capacity toward tumor by elevated prostaglandin E2 levels in mice bearing Lewis lung carcinoma.

The capacity to generate cytotoxic cells toward Lewis lung carcinoma (LLC) in mixed cultures of stimulator LLC and responder spleen cells of LLC-bearing C57BL/6 mice was monitored during the course of tumor growth. The cytotoxic response of mice bearing tumors that were not yet palpable was enhanced. However, as palpable tumors developed and tumor growth progressed, their cytotoxic capacity became suppressed. Concurrent with this decline in cytotoxic capacity, there was an increase in systemic immunoreactive prostaglandin E2 (PGE2) concentrations in tumor-bearing mice. Administration of indomethacin, a prostaglandin synthesis inhibitor, to LLC-bearing mice prevented the rise in PGE2 concentrations and the suppression in cytotoxic capacity toward LLC. A relationship between the elevated immunoreactive PGE2 levels, suppression in cytotoxic capacity, and progressive tumor growth was indicated when administration of indomethacin to tumor-bearing mice also reduced the rate of tumor development.