title: Glucocorticoids produced during exercise may be necessary for optimal virus-induced IL-2 and cell proliferation whereas both catecholamines and glucocorticoids may be required for adequate immune defense to viral infection.
abstract: Prolonged, exhaustive exercise has been associated with impaired immune responsiveness and increased susceptibility to infection. We have shown that one bout of exercise to fatigue followed by viral challenge increases mortality. Stress hormones such as corticosteroids and catecholamines have been suggested as potential mediators of exhaustive exercise-induced immunosuppression. The purpose of this study was to determine whether the administration of pharmacological agents to block the effect of catecholamines or corticosteroids would minimize the immunosuppression associated with this type of exercise. Mice either exercised to fatigue or were exposed to control conditions, and mice received an i.p. injection of either nadolol (beta-adrenergic receptor antagonist), RU486 (glucocorticoid type II receptor antagonist), or vehicle. Fifteen minutes post-exercise, mice were exposed to viral infection (Herpes simplex virus; HSV) via an intranasal route, and cells were collected 3 days post-infection. The results showed that exercise suppressed HSV-specific cell proliferation, HSV-specific IL-2, and IFN-gamma, but did not alter these same immune parameters when the mitogen ConA was used to stimulate cells. In addition, exercise reduced NK cell cytotoxicity, alveolar cell TNFalpha, and peritoneal IL-1beta, but did not affect IL-10. The pharmacological blockade did not attenuate the exercise-associated immunosuppression. In fact, RU486 treatment exacerbated the exercise-induced decline in HSV-induced IL-2 production and cell proliferation. RU486 and nadolol treatment also tended to decrease IL-10, IFN-gamma, TNFalpha (nadolol only), and IL-1beta (RU486 only) in both exercise and control mice, suggesting that stress hormones may be necessary during infection for optimal responsiveness. These findings suggest that suppression of immune defenses during viral infection persists for at least 3 days post-exercise, and stress hormones may be essential for optimal immune defense to viral challenge, rather than detrimental.
authors.affiliation: Immunobiology Program, Department of Health and Human Performance, Iowa State University, Ames, 50011-1160, USA. mkohut@iastate.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Kohut
authors.forename: A E
authors.initials: AE
authors.lastname: Martin
authors.forename: D S
authors.initials: DS
authors.lastname: Senchina
authors.forename: W
authors.initials: W
authors.lastname: Lee
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002395:Catecholamines / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D005938:Glucocorticoids / Q000378:metabolism* / Q000502:physiology*; D006561:Herpes Simplex / Q000276:immunology / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; D002395:Catecholamines; D016207:Cytokines; D005938:Glucocorticoids; D007376:Interleukin-2; D008934:Mitogens; D003208:Concanavalin A