Immunoregulation of antitumor response; differential secretion of arachidonic acid metabolites by macrophages during stimulation in vitro with BCG and Corynebacterium parvum.

The level of arachidonic acid (AA) metabolites in the supernatants of cultured peritoneal exudate cells (PEC) were studied under various conditions using BCG and Corynebacterium parvum as stimulators. The metabolite levels were analyzed by thin layer chromatography (TLC). The degree of macrophage cytotoxic/cytostatic activity was dependent on the dose and character of stimulators used and the source of macrophages. The application of microcytotoxicity assay for the evaluation of tumor cell lysis (lung sarcoma SaL-1) in vitro revealed that peritoneal macrophages from healthy and tumor bearing BALB/c mice may affect the degree of antitumor response. In the supernatants of cultured PEC from tumor bearing mice AA level increased (by 10-fold) in comparison with PEC from healthy mice. Stimulation with BCG induced over a double level of AA in PEC isolated from tumor bearing mice nonstimulated or stimulated with C. parvum. A lower level of prostaglandins (PGs) was found in the supernatants of cultured PEC isolated from healthy mice (stimulated and non-stimulated), but the highest level of PGs was observed in the supernatants of cultured PEC isolated from tumor bearing mice stimulated with BCG. The unique metabolite of AA was found only in the supernatants from nonstimulated PEC from tumor bearing mice. PEC from tumor bearing mice produced metabolites of AA which were not detected in control group. These results suggest that macrophages also play a regulatory role by secretion of AA. This process can be modified by bacterial antigens.