Macrophage depletion and manipulation of enhanced immune response in an animal model of bladder cancer.
In a transplantable model of bladder cancer the inhibition of tumor growth by polyinosinic:polycytidylic acid (poly(I:C], concomitant stimulation of natural killer cell activity, and inhibition of both effects by prior inoculation with anti-interferon antiserum have been previously observed. The possible role of macrophages in these interactions is explored. Depletion of peritoneal macrophages by silica at concentrations that did not markedly depress natural killer cell activity was found to inhibit the enhancement of natural killer cell activity by subsequent in vivo poly(I:C) inoculation. Inoculation with silica also seemed to abrogate the tumor inhibitory effect of poly(I:C) treatment. To determine whether effects of poly(I:C) on natural cytotoxicity and tumor growth were mediated through production of interferon, anti-interferon antiserum (alpha-IF) was inoculated prior to poly(I:C) therapy. Tumor growth appeared to be uneffected by this maneuver even though poly(I:C)-induced enhancement of natural cytotoxicity was inhibited. Taken together, both macrophages and interferon may play a pivotal role in the immune response in both a stimulatory and a suppressive capacity. Additional study on such influences may be important if in vivo manipulation of these regulatory effects is to be accomplished successfully.
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D007372:Interferons / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D012822:Silicon Dioxide / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000276:immunology*
D012822:Silicon Dioxide; D007372:Interferons; D011070:Poly I-C