Abrogation of B16 melanoma metastases by long-term low-dose interleukin-6 therapy.
We investigated the antitumor effects of human recombinant interleukin-6 (hrIL-6) on the highly metastatic B16 melanoma clone F10.9. These tumor cells were found to have very low levels of IL-6 receptors and in vitro IL-6 had no effect on cell proliferation or on the expression of MHC class I antigens. However, in vivo IL-6 was active against the metastatic growth of this tumor in mice, presumably through indirect immune effects. Low-dose IL-6 (1-10 micrograms/day), in three daily injections, 4 days a week, for 3 weeks, strongly inhibited the formation of experimental lung metastases following intravenous tumor cell inoculation. IL-6 therapy could be started even 10 days after tumor injection, when metastases are already established. Moreover, IL-6 treatment of mice bearing F10.9 tumors in the footpads resulted in complete protection against pulmonary spontaneous metastasis and in long-term survival. Histology confirmed the absence of micrometastases in most of the IL-6-treated animals. Analysis of the cytolytic activity of splenocytes at different times during therapy of tumor-bearing mice revealed significant lysis (up to 42%) of the melanoma F10.9 cells in the mice receiving IL-6 but not in the control mice.
Katz
A
A
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shulman
L M
LM
Porgador
A
A
Revel
M
M
Feldman
M
M
Eisenbach
L
L
D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007167:Immunotherapy; D015850:Interleukin-6 / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000556:secondary* / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000032:analysis; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins