Interleukin-6 inhibition reduces reperfusion injury in NSTEMI

In a placebo-controlled randomized trial, Ola Kleveland has investigated the effect of the interleukin-6 receptor antagonist tocilizumab in patients with non-ST-elevation myocardial infarction.


MAIN RESULTS:

  1. Interleukin-6 inhition with tocilizumab lowers plasma levels of hs-CRP and troponin T in patients with NSTEMI.
  2. Tocilizumab treatment in NSTEMI does not affect coronary microcirculation or endothelial function.
  3. Tocilizumab affects the levels of the cytokines IP-10 and MIP-1β following NSTEMI.

THESIS DEFENCE:

Thesis: Interleukin-6 receptor inhibition in non-ST-elevation myocardial infarction: Results from a randomized clinical trial
Candidate: Ola Kleveland
Time: February 21 at 12:15
Place: St. Olavs Hospital, The Laboratory Center: Auditorium LA24
Link to university website (in Norwegian)


SUMMARY:

(1) A single dose of tocilizumab reduces inflammation and PCI-related reperfusion injury without serious side effects in patients with non-ST-elevation myocardial infarction. Tocilizumab inhibits the effect of the pro-inflammatory cytokine interleukin-6, and this is the first study to test the drug in coronary patients.

In total, the researchers analyzed blood samples  from 117 patients who were randomly allocated to treatment with one dose tocilizumab or placebo. Tocilizumab reduced the levels of high-sensitive C-reactive protein (hs-CRP) by more than half, and the effect was most pronounced in PCI-treated patients. In this group, tocilizumab also prevented an increase in troponin T the first day following coronary angiography.

(2) There was no beneficial effect of tocilizumab on coronary artery endothelial function or microvascular circulation. A single dose of the drug actually increased the levels of VCAM-1, a marker of endothelial activation, compared to placebo. Changes in endothelial function and coronary microvascular circulation were measured in 42 patients over six months following treatment for NSTEMI.

(3) Tocilizumab had marginal impact on the levels of 25 of the 27 cytokines that were measured in NSTEMI patients. A lot of these cytokines are pro-inflammatory, and the levels are associated with atherosclerosis and cardiovascular disease. The only molecules that were significantly affected were IP-10 and MIP-1β.


REFERENCES:

(1) Kleveland, O., Kunszt, G., Bratlie, M., Ueland, T., Broch, K., Holte, E., Michelsen, A. E., Bendz, B., Amundsen, B., Espevik, T., Aakhus, S., Damås, J. K., Aukrust, P., Wiseth, R., & Gullestad, L.(2016). Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trialEuropean heart journal37(30), 2406-2413.

(2) Holte, E., Kleveland, O., Ueland, T., Kunszt, G., Bratlie, M., Broch, K.,  Michelsen, A. E., Bendz, B., Amundsen, B., Aakhus, S., Damås, J. K., Gullestad, L., Aukrust, P., & Wiseth, R. (2017). Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarctionHeart, heartjnl-2016.

(3) Kleveland, O., Ueland, T., Kunszt, G., Bratlie, M., Yndestad, A., Broch, K., Holte, E., Ryan, L., Amundsen, B. H., Bendz, B., Aakhus, S., Espevik, T., Halvorsen, B., Mollnes, T. E., Wiseth, R., Gullestad, L., Aukrust, P., & Damås, J. K. (2018). Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarctionInternational journal of cardiology271, 1-7.