Immune Modulation by Ischemic Pre-conditioning in Healthy Individuals: Intracellular Signalling in Regulatory Cells (KONDI-immun)

Immune Modulation by Ischemic Pre-conditioning in Healthy Individuals: Intracellular Signalling in Regulatory Cells

Immune Modulation by Ischemic Pre-conditioning in Healthy Individuals: Intracellular Signalling in Regulatory Cells

The aim of the study is to investigate how phosphorylation of STAT3, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) reacts to remote ischemic conditioning (rIC) in healthy humans, which could point to mechanisms by which rIC may protect against ischemia-reperfusion injury (IRI), and if rIC affects immune reactivity.

In rIC brief episodes of non-lethal ischemia and reperfusion in one vascular bed, tissue or organ, has shown to have protective effects against IRI in various organs. The protective effect of rIC seems convincing, but to date it is not clear which mechanisms give rIC its effects, and why effects are absent in some situations. Effects of rIC on the immune system are also not clear, but important if rIC is used in transplantation and autoimmunity settings, and also in regards to infection risk. Patients studied have often been given medical treatment and/or have comorbidities affecting the results. This project will measure how intracellular phosphorylation of STAT3, p38 MAPK, ERK and AKT, inflammatory cell patterns and cytokine production react to rIC in healthy humans, and potentially give a better understanding of the mechanisms that mediate the protective effects of rIC. The intracellular mediators studied are involved in the initiation of cytokine production and regulate apoptosis and activation of the inflammatory cells. An altered balance between leucocytes and their mediators could be of importance for rIC effects, particularly in transplantation and autoimmunity, and this will be elucidated in our study. As a secondary end point the investigators will measure the effect of rIC on pulse variability and blood pressure using a non-invasive device, since evidence regarding these aspects is sparse, although documented positive effects of rIC have primarily been on the heart and vascular system.

The participants will have the cuff attached to the arm, however not be inflated for the 4 cycles of remote ischemic conditioning: 1 cycle is 5 minutes of inflation followed by 5 minutes of deflation. The ischemic reperfusion injury was induced by cuff inflation by the Single Cuff Tourniquet 8000 to 200 mmHg in the arm for 20 minutes followed by reperfusion for 15 minutes.

The blood supply to the distal part of the arm will be occluded by inflation of a single cuff to 200mmHg, by the help of the Single Cuff Tourniquet 8000, for 5 minutes separated from 5 minutes of deflation, a cycle that happens 4 times in total. The ischemic reperfusion injury was induced by cuff inflation to 200 mmHg in the arm for 20 minutes followed by reperfusion for 15 minutes.

If randomized to ischemic conditioning the cuff will be inflated as stated before. If randomized to non-ischemic conditioning the cuff will not be inflated.

The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.

The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.

The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.

The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.

Inclusion Criteria: Healthy and well Exclusion Criteria: Smoker. Taking regular medication. Any acute, chronic or systemic disease No hard physical exercise 72 hours prior to study participation. No alcohol or caffein-containing drinks 24 hours prior to study participation. Fasted for at least 6 hours prior to study participation.