Immunoregulatory cytokine release in rat spleen cell cultures after treatment with bleomycin and its analogues in vivo.
We have studied the immunological effects that accompany a change in the chemical structure of a group of antineoplastic antibiotics by comparing the immunoregulatory cytokine release during mitogen-stimulated spleen cell culture after in vivo drug treatment. Whereas bleomycin and peplomycin increased cytokine levels in culture supernatants when compared with supernatants from untreated control rat spleen cell cultures, liblomycin generally reduced cytokine levels under the same culture conditions. We then compared these results with the antitumor effects of equivalent doses of the three drugs against a highly antigenic rat fibrosarcoma, KMT-17, both in vivo and in vitro. The results suggest that the immunoaugmenting effects of these antitumor antibiotics are essential for an optimal antitumor effect in vivo, and that these effects can be drastically altered by modification of the chemical structure of the drugs employed.
Micallef
M
M
Laboratory of Pathology, Cancer Institute, Sapporo, Japan.
Hosokawa
M
M
Shibata
T
T
Nakane
A
A
Yang
Z B
ZB
Minagawa
T
T
Kobayashi
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology* / Q000031:analogs & derivatives; D016207:Cytokines / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D005434:Flow Cytometry; D007372:Interferons / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017663:Peplomycin; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D017663:Peplomycin; C054113:liblomycin; D007372:Interferons