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 i nterleukin 6 (IL-6) levels, and the metastatic process in C57BL/6 mice after intravenous inoculation of B16-BL6 melanoma cells. Bioactive TN F was not detectable in the sera of inoculated mice, but these animals did show higher TNF levels following intraperitoneal challenge with l ipopolysaccharide (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 (afte r LPS challenge) and IL-6 levels in inoculated animals. Lung metastase s at 7-14 days were reduced, compared to human IgC-injected control an imals, but this effect was lost al day 21 postinoculation. The results suggest that the reduction in the number of metastases may be related to the effect of blocking TNF activity.