Indomethacin enhancement of spleen-cell responsiveness to mitogen stimulation in tumorous mice.
Spleen cells removed from C57Bl/6J mice bearing a methylcholanthrene-induced fibrosarcoma (MC-16) demonstrate suppressed responsiveness of phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) induced mitogenesis as compared to non-tumorous mice. A similar depression of PHA-induced mitogenesis was observed with spleen cells from C3H/HeJ mice bearing syngeneic mammary adenocarcinomas (C3HBA). The administration of indomethacin, a non-competitive irreversible prostaglandin (Pg) synthesis inhibitor, (75 or 100 mug/mouse, IP) on an alternate day basis to groups of tumor-bearing mice of both strains, significantly enhanced immune cell responsiveness to mitogenic stimulation. The addition of indomethacin (10 mug/ml) to cultures of spleen cells from these tumor-bearing mice, as well as to DBA/1J mice bearing the Cloudman S-91 melanoma, enhanced spleen-cell responsiveness to mitogen-induced DNA synthesis by as much as 156%. Indomethacin administration in vivo or in vitro had no significant effect on mitogen-induced DNA synthesis of spleen cells from non-tumor-bearing animals. It is hypothesized that tumors, or tumor-cell antigens, increase Pg production of a population of spleen cells, and that the increased Pg content of the spleen may be important in controlling immune responsiveness in mice.
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D037102:Lectins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008938:Mitosis / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D013154:Spleen / Q000187:drug effects*
D037102:Lectins; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D011460:Prostaglandins F; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D007213:Indomethacin