Exercise training has a profound impact on immunity, exerting a multitude of positive effects in indications such as immunosenescence,
cancer,
viral infections and inflammatory diseases. The immune, endocrine and central nervous systems work in a highly synergistic manner and it has become apparent that
catecholamine signaling through leukocyte β-
adrenergic receptors (β-ARs) is a key mechanism by which exercise mediates improvements in immune function to help mitigate numerous disease conditions. Central to this is the preferential mobilization and redistribution of effector lymphocytes with potent anti-viral and anti-
tumor activity, their interaction with muscle-derived
cytokines, and the effects of
catecholamine signaling on mitochondrial biogenesis, immunometabolism and the resulting inflammatory response. Here, we review the impact of acute and chronic exercise on
adrenergic regulation of immunity in the context of aging,
cancer,
viral infections and inflammatory disease. We also put forth our contention that exercise interventions designed to improve immunity, prevent disease and reduce
inflammation should consider the
catecholamine-AR signaling axis as a therapeutic target and ask whether or not the
adrenergic signaling machinery can be 'trained' to improve immune responses to stress, disease or during the normal physiological process of aging. Finally, we discuss potential strategies to augment leukocyte
catecholamine signaling to boost the effects of exercise on immunity in individuals with desensitized β-ARs or limited exercise tolerance.