we use lentivirus to deliver shRNA to IL-6 in mesenchymal cells. nice results, not sure if you can culture t-cells long enough to incorporate viral DNA though

If not using siRNA, I will suggest to use inhibitor to inhibit the downstream pathways of IL6 signaling pathway.

stattic is a potent inhibitor of JAK/Stat signaling of all ErB ligands

IL-6 signaling is predominantly mediated by STAT3 pathways. Hence, STAT3 inhibitor, static could be used to block the IL-6 signaling in CD8 T-Cells.

You could block the down stream IL-6 signalling pathway (JAKs/STAT3) with small molecule inhibitors but the obvious down side would be that you would also affect other cytokine signalling pathways.

So you are trying to avoid antibodies in general? Otherwise you could try to target cellular gp130. Or Stat3 as mentioned above. Or sIL6R+gp130_Fc to bind IL-6.

Knockdown (siRNA, shRNA) of the cognate IL6-R is of course the most specific. But as an alternative, you could use a cocktail of a MEK, a PI3K and a STAT pathway inhibitor. That should do it.

JAK2/STAT3 inhibitor is a good idea, of course if you don't wanna use siRNA!

Dear Md Aziz, dear Catharien,

Static is interesting. Do you have experience with the use of the inhibitor?

We like to use an inhibitor (as specific as possible) for pre-incubation of CD8+ T cells before coculture with PBMC of a second donor. Since, we have to prevent the unwanted effects of these inhibitor on signaling in PBMC and have to prevent activation of CD8+ T cells (one general result of nucleofection in our hands) a blocking inhibitor as specific as possible would be the best.

Hi Dr. Helmut,

Following link shows the article where I used static in macrophages. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027685

Thanks.