Effect of blocking TNF on IL-6 levels and metastasis in a B16-BL6 melanoma/mouse model.
We studied the relationship between tumour necrosis factor (TNF) and interleukin 6 (IL-6) levels, and the metastatic process in C57BL/6 mice after intravenous inoculation of B16-BL6 melanoma cells. Bioactive TNF was not detectable in the sera of inoculated mice, but these animals did show higher TNF levels following intraperitoneal challenge with lipopolysaccharide (LPS) compared to control animals. Serum IL-6 levels were increased in inoculated animals. Injection of a hybrid molecule (p55-sf2) composed of the human p55 TNF receptor extracellular domain coupled to a human constant region backbone, decreased serum TNF (after LPS challenge) and IL-6 levels in inoculated animals. Lung metastases at 7-14 days were reduced, compared to human IgG-injected control animals, but this effect was lost at day 21 postinoculation. The results suggest that the reduction in the number of metastases may be related to the effect of blocking TNF activity.
Cubillos
S
S
Laboratorio de Fisiopatologia, Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas, Venezuela.
Scallon
B
B
Feldmann
M
M
Taylor
P
P
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007167:Immunotherapy; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*
D015703:Antigens, CD; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha