Systemic β 1 -Adrenergic Receptor Blockade Augments NK-Cell Mobilization In Response To Acute Exercise In Humans

Abstract

PURPOSE: Recent research has demonstrated that the release of catecholamines, myokines, and the mobilization and redistribution of effector lymphocytes (e.g. NK-cells) with each bout of exercise plays a mechanistic role in the anti-tumor effects provided by regular exercise. We tested the hypothesis that blocking the β1-AR in vivo would increase catecholamine signaling toward the β2-AR to augment NK-cell mobilization in response to a single exercise bout. METHODS: Thirty healthy subjects (ages 22 - 43) completed a single 30-minute bout of steady state exercise on a cycle ergometer at +10 to +15% of their predetermined lactate threshold to determine the number of NK-cells mobilized to blood with exercise. Eighteen of these subjects then participated in a randomized double-blind controlled trial with a cross-over design, whereby a placebo, a non-preferential β1+β2-antagonist (80 mg nadolol), or a preferential β1-antagonist (10 mg bisoprolol) was ingested orally 3 hours before a 30-minute exercise bout performed on separate days. Blood samples were collected before and immediately after exercise for the enumeration of effector lymphocytes (NK-cells, γδ T-cells and CD8+ T-cells) by flow cytometry. RESULTS: The median number of NK-cells mobilized to blood with exercise was Δ524 cells/μL, with those subjects below the median demonstrating a smaller epinephrine response to exercise than those above the median (Δ0.05 ± 0.03 vs Δ0.13 ± 0.08 ng/mL; p < 0.05). Larger numbers of NK-cells were mobilized with exercise in the bisoprolol trial (Δ703.8 ± 352.2 cells/μL) compared to the placebo trial (Δ537.9 ± 198.1 cells/μL; p < 0.05), both of which were larger than the nadolol trial (Δ285.1 ± 165.6 cells/μL; p < 0.05). Bisoprolol did not augment the mobilization of γδ T-cells or CD8+ T-cells relative to placebo. 44% of subjects who mobilized less than Δ524 NK-cells/μL with exercise in the placebo trial were able to mobilize >Δ524 NK-cells/μL after ingesting bisoprolol (n = 4). CONCLUSION: Systemic β1-AR blockade augments NK-cell mobilization in response to acute exercise. These findings may have implications for cancer patients on cardioprotective β-blockers and also provide insights on how certain β-AR antagonists may enhance or inhibit immune responses to exercise.