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Sunday, January 25, 2015 12:54:00 AM
INF-alpha is VERY immunostimulatory. Always has been. That's why it's used been used for decades to fight Hepatitis C (Interferon alpha 2a i.e. "Pegasys").
While I agree that IL-1 and IL-6 are essentially immunosuppressive (they are in fact Th2 promotors of antibody-mediated immunity), IL-12 definitely is not.
Check the article below on INF-alpha:
RESULTS:
Treatment of peripheral blood mononuclear cells with a combination of CpG ODNs and IFN-alpha resulted in enhanced cytotoxicity and activation of natural killer cells. Administration of CpG ODNs plus IFN-alpha elicited superior antitumor activity in a murine model of B16 melanoma compared with either agent alone.
"INF-alpha resulted in enhanced cytotoxicity." "Activation of natural killer cells." Sounds pretty good to me. Not immunosuppressive at all.
IL-12 immunostimulatory for dendritic cells
Systemic IL-12 administration modulates dendritic cells to overcome the immunosuppressive microenvironment of the liver
Again, you say IL-12 is immunosuppressive. Far from it, my friend.
As for Transforming Growth Factor B (your TGF-B), it is essentially immunostimulatory of Tregs, but more importantly, it shifts to Th1 cell-mediated attack when in the presence of IL-12. This combination prompts your macrophages to release nitric oxide. (Again, more proof that IL-12 is immunostimulatory).
Furthermore, the cells activated in the presence of both TGF-ß and IL-12, and not of TGF-ß only, stimulated macrophages to produce nitric oxide. Altogether, these results indicate that IL-12 is a superior cytokine that has the ability to skew the already ongoing TGF-ß-dependent iTreg or Th17 developmental program into Th1-like direction.
As you know, Th1 immunity is CELL-mediated immunity, which is what you want against cancer.
Hope this helps.
Best,
Joe
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