Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity

Abstract

Exercise elicits an immunological "danger" type of stress and inflammatory response that, on occasion, becomes dysregulated and detrimental to health. Examples include anaphylaxis, exercise-induced asthma, overuse syndromes, and exacerbation of intercurrent illnesses. In dangerous exercise, the normal balance between pro- and anti-inflammatory responses is upset. A possible pathophysiological mechanism is characterized by the concept of exercise modulation of previously activated leukocytes. In this model, circulating leukocytes are rendered more responsive than normal to the immune stimulus of exercise. For example, in the case of exercise anaphylaxis, food-sensitized immune cells may be relatively innocuous until they are redistributed during exercise from gut-associated circulatory depots, like the spleen, into the central circulation. In the case of asthma, the prior activation of leukocytes may be the result of genetic or environmental factors. In the case of overuse syndromes, the normally short-lived neutrophil may, because of acidosis and hypoxia, inhibit apoptosis and play a role in prolongation of inflammation rather than healing. Dangerous exercise demonstrates that the stress/inflammatory response caused by physical activity is robust and sufficiently powerful, perhaps, to alter subsequent responses. These longer term effects may occur through as yet unexplored mechanisms of immune "tolerance" and/or by a training-associated reduction in the innate immune response to brief exercise. A better understanding of sometimes failed homeostatic physiological systems can lead to new insights with significant implication for clinical translation.

Short-term blackcurrant extract consumption modulates exercise-induced oxidative stress and lipopolysaccharide-stimulated inflammatory responses

“…This may also account for the differential temporal cytokines secretion pattern observed after exercise in this study and by others (47). Furthermore, it is feasible that exercise-induction of an acute inflammation may be an important step in the activation of appropriate adaptive immune responses (14), which is in contrast to the chronic subclinical inflammation observed in some athletes undergoing long-term strenuous training regimens, which results in immune suppression (9).…”

“…Exercise-induced oxidative stress (11,48,50), either via reactive oxygen species (ROS)-dependent (2, 14) or -independent (23) mechanisms, appears to be an important modulator in a number of adaptive responses to exercise: upregulation of endogenous antioxidant systems (42, 18), modulation of muscle function (17), improved efficacy of influenza immunization (15), and enhanced immune surveillance (14). Characterization of how exercise modulates the immune system in untrained individuals as well as athletes shows how the type, intensity, and duration of exercise affects the immune responses to pathogenic agents, such as bacterial endotoxin LPS (9,12,16). In addition to regular exercise, the ingestion of antioxidant supplements or foods high in antioxidants and vitamins, such as C and E, have become commonplace in efforts to maintain health and prevent chronic oxidative stressassociated aliments (5).…”

A brief bout of exercise alters gene expression and distinct gene pathways in peripheral blood mononuclear cells of early- and late-pubertal females

“…There are mounting data that leukocytes are not only involved in eradicating pathogens but also play a role in wound repair, muscle growth, other key developmental processes, and childhood diseases like asthma and arthritis (12,13,27,31). Moreover, brief exercise can trigger bronchoconstriction and anaphylaxis, both serious conditions in which the inflammatory response appears to be dysregulated (7). Our knowledge of the acute effects of exercise on leukocyte gene expression in humans is still rudimentary.…”

Gastritis and Peptic Ulcer Diseases in Dogs: A Review

“…In humans oxidative stress occurs during exercise leads to decrease gastric and mesenteric blood flow ( Qamar et al, 1987;Mastaloudis et al, 1994;Hinchcliff et al, 2000;Otte et al, 2001;Radak et al, 2003) along with mitochondrial electron transport chain inefficiency during respiration leading reperfusion injury mediated by ROS. In the disease condition, exercise has been activated to pro-inflammatory cascades which are able to trigger the leukocytes (Cooper et al, 2007).…”