Recombinant tumor necrosis factor alpha inhibits growth of methylcholanthrene-induced sarcoma and enhances natural killer activity of tumor-infiltrating lymphocytes in aging rats.
The effect of recombinant human tumor necrosis factor alpha (rHuTNF-alpha) on the growth of immunogenic, methylcholanthrene-induced sarcoma (MC-Sa) and natural killer (NK) cell activity of tumor-infiltrating lymphocytes (TIL) in adult and aging rats was investigated. In both groups of animals the growth of transplantable MC-Sa was markedly and similarly inhibited by multiple intratumoral (i.t.) injections of rHuTNF-alpha. This effect was accompanied by stimulation of NK activity of tumor-infiltrating lymphocytes in adult as well as in aging rats. Studies in vitro demonstrated additionally that rHuTNF-alpha was a potent stimulator of NK but not of ADCC (antibody-dependent cellular cytotoxicity) activity of spleen lymphocytes from healthy animals. Our results indicate that the antitumor effect of TNF-alpha is comparable in adult and in aging rats bearing immunogenic MC-Sa. The inhibition of MC-Sa growth may be attributed not only to the TNF-alpha-induced necrosis of the neoplastic tissue but also to the in vivo stimulatory effect of this cytokine upon the NK-type function of lymphocytes infiltrating the tumor mass.
Department of Pathophysiology, Institute of Rheumatology, Warsaw, Poland.
M
M
Ziółkowska
J J
JJ
Nowak
M
M
Janiak
A
A
Ryzewska
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000375:Aging / Q000276:immunology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D008297:Male; D008748:Methylcholanthrene; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; D008748:Methylcholanthrene