Immune and Neuroendocrine Alterations in Marathon Runners

Marathon running is a stressful event that can significantly affect virtually any of the physiologic systems of a runner. The goal of this study was to investigate effects of marathon running on human immune and neuroendocrine parameters and their interaction. Blood samples were collected from 15 male runners (38.3 ± 6.9 years) 18 hours before finish time, then within 20 minutes (0h), 1 hour, 24 hours, 48 hours, 5 days, and 8 days after the marathon. Complete blood count, secretion of cytokines in mitogenactivated cell culture and plasma, and plasma concentration of β-endorphin, Adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) were analyzed. Significant increase in granulocyte and MID-cell count and lymphopenia were seen immediately after the marathon. Secretion of interleukin (IL)-2 and interferon (IFN)-γ significantly declined at 0 and 1 hour after the marathon. Secretion of TNF-α declined at 0 hours and remained suppressed until 5 days. Suppression in the secretion of IL-1β was observed at 48-hour and 5-day intervals. Activated secretion of IL-6 decreased at 24 and 48 hours. Peak concentrations of ACTH, cortisol, β-endorry cytokines to marathon running has been studied intensively.5,13-18 However, there is limited and often contradictory information pertaining to cytokine-promoted cell-mediated (type-1) versus humoral (type-2) immune response to endurance running or exercise. Weinstock et al.19 showed a significant decrease in mitogen-activated secretion of interleukin (IL)-2 and interferon (IFN)-γ one hour after exhaustive competitive exercise (sprint triathlon). Similarly, a significant decrease of endotoxin-B induced IFN-γ secretion was observed 30 minutes after exhaustive ergometer exercise.20 At the same time, no changes in the plasma concentration of IFN-γ, IL-1∫, IL-12, IFN-α, and tumor necrosis factor (TNF)-α were registered after the marathon in the study Suzuki et al. It was accompanied by a significant increase in concentration of IL-10, although concentrations of IL-4 and TGF-β were unaffected by the race.6 In contrast, a significant elevation of plasma IL-2 level without changes in IL-1α plasma level was observed 16 hours after completing the marathon, as reported in the study of Castell et al.21 Moreover, prolonged physical exercise resulted in a significant decrease in the relative percentage and absolute number of Tcells (CD3+) and NK-cells (CD16+), which are major producers of type-1 and type-2 cytokines.22 Physiologic and psychological stress factors of exhaustive endurance exercise may affect the cell mediated-humoral immune equilibrium through perturbations in the neuroendocrine system. One of the major events that occurs during the neuroendocrine stress reaction to a marathon run is the activation of the hypothalamic–pituitary–adrenocortical (HPA) axis.23-26 Dramatic elevation of ACTH, endorphins, and cortisol is a classic representation of the HPA axis response to a prolonged bout of exercise.27-29 Cortisol is well known for its anti-inflammatory and immunosuppressive properties,30,31 but this stress hormone is also able to unequally modulate cell-mediated and humoral immune reactions.32-34 Thus, stress (marathon)-induced neuroendocrine mediators and especially corticosteroids may alter cell-mediated or humoral equilibrium and therefore result in increased susceptibility to infections, autoimmune reactions and allergies. This study was designed to investigate effects of marathon-associated stressors on cell-mediated versus humoral and antiinflammatory versus proinflammatory equilibrium as well as their correlations to neuroendocrine response. We measured secretion of cytokines, which support cellmediated reactions or favor humoral immunity and are involved in inflammatory mechanisms. Additionally, we assessed plasma concentrations of hormones to investigate their involvement in the stress-associated immune alterations. MATERIALS AND METHODS Subjects and Experimental Design This study presents data from two marathon races. Eight runners participated in the White Rock (WR) marathon race in December 1996 (Dallas, Tex), and seven runners participated in the Cowtown (CT) marathon in February 1997 (Forth Worth, Vol. 3, No. 4, Fall 2003 • The Journal of Applied Research 484 Table 1. Demographic and Fitness Data for Runners Who Participated in the Studies Marathon Age (yrs) Marathon Best time Body wt (kg) Training time (h:min) (h:min) (miles/wk)