Reduction of Myocardial Ischemia-Reperfusion Injury by Inhibiting Interleukin-1 Alpha.

BACKGROUND: Interleukin-1α (IL-1α) released by dying cells is an alarmin that activates the innate immunity. We hypothesized that after myocardial ischemia-reperfusion (I/R) injury, IL-1α amplifies the myocardial damage by activating the inflammasome and caspase-1. METHODS: Adult male CD1 mice were used. The left anterior descending coronary artery was ligated for 30 minutes, after 24 hours of reperfusion. An IL-1α blocking antibody (15 µg/kg intraperitoneally) or matching vehicle was given after reperfusion. A subgroup of mice underwent sham surgery. We assessed the effects of IL-1α blockade on caspase-1 activity, infarct size, cardiac troponin I serum levels, and left ventricular fractional shortening, 24 hours after I/R. RESULTS: I/R led to inflammasome formation, and IL-1α blockade significantly reduced inflammasome formation, reflected by a >50% reduction in caspase-1 activity versus vehicle (P = 0.03). IL-1α blockade also reduced the infarct size (-52% infarct expressed as percentage of area at risk, and -79% for cardiac troponin I serum levels, P < 0.001 vs. vehicle) and preserved the left ventricular fractional shortening (31 ± 3% vs. 25 ± 2%, P < 0.001 vs. vehicle). CONCLUSION: IL-1α blockade after I/R reduces the inflammasome activation, decreases the infarct size, and preserves the left ventricular function. IL-1α blockade may therefore represent a novel therapeutic strategy to reduce I/R injury.

Beneficial effects of exercise on chemotherapy-induced peripheral neuropathy and sleep disturbance: A review of literature and proposed mechanisms.

The goal of this narrative review is to evaluate the literature regarding exercise training as a therapy to prevent or mitigate deleterious side effects of chemotherapy, specifically peripheral neuropathy and sleep disturbances and to make concrete recommendations for implementation for the practicing oncologist. A literature search was conducted for studies that included an exercise intervention to be implemented for patients undergoing or previously treated with chemotherapy along with an analysis of its effect on either chemotherapy-induced peripheral neuropathy (CIPN) or chemotherapy-induced sleep disturbances. Studies were subsequently analyzed and summarized in order to determine the overall promise of exercise as a therapy in this setting. Five studies met inclusion criteria to be assessed with regard to the effect of exercise on CIPN and eight were included for sleep disturbances. Exercise was found to be a significantly beneficial therapy in preventing, mitigating, or improving the symptoms of CIPN and sleep disturbances in cancer patients in the majority of studies evaluated. Exercise is an effective intervention and should be specifically prescribed concurrently with chemotherapy to maximize potential of avoiding these debilitating side effects, which significantly and negatively impact quality of life in cancer survivors.