In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1 beta. II. Mechanism of inhibition: the role of polymorphonuclear leukocytes.
Recombinant human interleukin 1 beta (IL 1 beta) inhibits growth of B16 melanoma in syngeneic C57BL/6 mice in a dose-dependent manner when given intratumorally, intradermally, or intramuscularly over a period of 5 to 7 days. Inhibition of tumor growth was rapid and measurable within 3 days after the initial injection and occurred regardless of the route of injection. However, only intratumoral (ITU) injections of IL 1 beta resulted in greater than 90% inhibition in tumor growth. This enhanced inhibition of tumor growth was not dependent on T or NK cells since inhibition of tumor growth occurred in nude and Beige mice. Also, a profound lymphopenia occurred in mice receiving IL 1 beta. Inhibition of tumor growth did correlate with an increase in the number of polymorphonuclear leukocytes (PMN's) in the circulation. However, only ITU injections of IL 1 beta increased the number of PMN's within the tumors. IM injections of IL 1 beta, while increasing the number of PMN's in the circulation, did not increase the influx of PMN's into the tumors. Furthermore, the transfer of PMN's directly into B16 tumors caused a 49% reduction in tumor growth without the presence of IL 1 beta. These results suggest that in vivo, PMN's may effectively control the growth of tumors and that IL 1 beta may increase this effectiveness by increasing the number of PMN's in the circulation and by locally stimulating the production of chemotactic factors for PMN's within the tumor.
Neville
M E
ME
Dupont, Medical Products Department, Glenolden, PA 19036.
Pezzella
K M
KM
Schmidt
K
K
Galbraith
W
W
Ackerman
N
N
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007375:Interleukin-1 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D009195:Peroxidase / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D009195:Peroxidase