Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin.
The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin.
DeSilva
M A
MA
Wepsic
H T
HT
Mizushima
Y
Y
Nikcevich
D A
DA
Larson
C H
CH
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002473:Cell Wall / Q000276:immunology; D002478:Cells, Cultured; D007108:Immune Tolerance / Q000187:drug effects*; D007213:Indomethacin / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D011912:Rats, Inbred ACI; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D001500:BCG Vaccine; D007213:Indomethacin