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Effect of blocking TNF on IL-6 levels and metastasis in a B16-BL6 melanoma/mouse model
S Cubillos1, B Scallon, M Feldmann
1Laboratorio de Fisiopatologia, Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas, Venezuela.
Abstract:
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.
Insights
Blocking tumour necrosis factor (TNF) reduced melanoma metastases in mice. This study investigated TNF and interleukin-6 (IL-6) roles in cancer spread, finding that inhibiting TNF activity decreased tumor development.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumour necrosis factor (TNF) and interleukin-6 (IL-6) are key cytokines implicated in inflammation and cancer.
- The role of these cytokines in the metastatic process, particularly in melanoma, requires further elucidation.
Purpose of the Study:
- To investigate the relationship between TNF and IL-6 levels and melanoma metastasis in a murine model.
- To evaluate the therapeutic potential of blocking TNF activity on metastasis reduction.
Main Methods:
- C57BL/6 mice were intravenously inoculated with B16-BL6 melanoma cells.
- Serum cytokine levels (TNF and IL-6) were measured after lipopolysaccharide (LPS) challenge.
- A hybrid TNF receptor molecule (p55-sf2) was administered to block TNF activity.
- Lung metastases were quantified at different time points post-inoculation.
Main Results:
- Inoculated mice exhibited elevated serum IL-6 levels and increased TNF response to LPS challenge.
- Administration of p55-sf2 molecule reduced serum TNF and IL-6 levels in inoculated mice.
- A significant reduction in lung metastases was observed at 7-14 days post-inoculation, but this effect diminished by day 21.
Conclusions:
- Blocking TNF activity with the p55-sf2 molecule demonstrates a transient inhibitory effect on melanoma lung metastasis.
- The findings suggest that TNF plays a role in promoting melanoma metastasis, and its blockade may offer a therapeutic strategy.
- Further research is warranted to optimize TNF inhibition for sustained anti-metastatic effects.