Overtraining syndrome (OTS) is a condition wherein an athlete is training excessively, yet performance deteriorates. This is usually accompanied by mood/behavior changes and a variety of biochemical and physiological alterations. Presently, there is no global hypothesis to account for OTS. The present paper will attempt to provide a unifying paradigm that will integrate previous research under the rubric of the cytokine hypothesis of overtraining. It is argued that high volume/intensity training, with insufficient rest, will produce muscle and/or skeletal and/or joint trauma. Circulating monocytes are then activated by injury-related cytokines, and in turn produce large quantities of proinflammatory IL-1beta, and/or IL-6, and/or TNF-alpha, producing systemic inflammation. Elevated circulating cytokines then co-ordinate the whole-body response by: a) communicating with the CNS and inducing a set of behaviors referred to as "sickness" behavior, which involves mood and behavior changes that support resolution of systemic inflammation: b) adjusting liver function, to support the up-regulation of gluconeogenesis, as well as de novo synthesis of acute phase proteins, and a concomitant hypercatabolic state; and c) impacting on immune function. Theoretically, OTS is viewed as the third stage of Selye's general adaptation syndrome, with the focus being on recovery/survival, and not adaptation, and is deemed to be "protective," occurring in response to excessive physical/physiological stress. Recommendations are made for potential markers of OTS, based on a systemic inflammatory condition.

The influence of carbohydrate (1 l/h of a 6% carbohydrate beverage), gender, and age on pro- and anti-inflammatory plasma cytokine and hormone changes was studied in 98 runners for 1.5 h after two competitive marathon races. The marathoner runners were randomly assigned to carbohydrate (C, n = 48) and placebo (P, n = 50) groups, with beverages administered during the races in a double-blind fashion using color codes. Plasma glucose was higher and cortisol was lower in the C than in the P group after the race (P < 0.001). For all subjects combined, plasma levels of interleukin (IL)-10, IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 rose significantly immediately after the race and remained above prerace levels 1.5 h later. The pattern of change in all cytokines did not differ significantly between the 12 women and 86 men in the study and the 23 subjects > or =50 yr of age and the 75 subjects <50 yr of age. The pattern of change in IL-10, IL-1ra, and IL-8, but not IL-6, differed significantly between the C and the P group, with higher postrace values measured for IL-10 (109% higher) and IL-1ra (212%) in the P group and for IL-8 (42%) in the C group. In conclusion, plasma levels of IL-10, IL-1ra, IL-6, and IL-8 rose strongly in runners after a competitive marathon, and this was not influenced by age or gender. Carbohydrate ingestion, however, had a major effect in attenuating increases in cortisol and two anti-inflammatory cytokines, IL-10 and IL-1ra.

Unaccustomed, eccentrically biased exercise induces trauma to muscle and/or connective tissue. Tissue damage activates an acute inflammatory response. Inflammation requires the effective interaction of different physiological and biological systems. Much of this is coordinated by the de novo synthesis of families of protein molecules, cytokines. The purpose of the present paper was to determine changes in blood levels of various cytokines in response to exercise-induced muscle damage that was effected using high-intensity eccentric exercise. Six healthy, untrained, college-age male subjects were required to perform the eccentric phase of a bench press and a leg curl (4 sets, 12 repetitions/set) at an intensity equivalent to 100% of their previously determined one-repetition maximum. Samples of blood were drawn at the following times: before exercise and 1.5, 6, 12, 24, 48, 72, 96, 120, and 144 h after exercise. These samples were analyzed for interleukins (IL): IL-1beta, IL-6, and IL-10; tumor necrosis factor-alpha; colony stimulating factors (CSF): granulocyte-CSF, macrophage-CSF, and GM-CSF; for cell adhesion molecules (CAM): P- and E-selectin, and intercellular cell adhesion molecule (ICAM-1), and vascular cell adhesion molecule (VCAM-1). Results were analyzed using a repeated-measures analysis of variance (P = 0.05). Compared to baseline values, IL-1beta was reduced (P = 0.03) at 6, 24, and 96-144 h after exercise; IL-6 was elevated (P = 0.01) at 12, 24, and 72 h after exercise; IL-10 was elevated (P = 0.009) between 72 and 144 h after exercise; M-CSF was elevated (P = 0.005) at 12 and 48-144 h after exercise; and P-selectin was reduced (P = 0.01) between 24 and 144 h after exercise. It is concluded that when high-intensity eccentric exercise is compared to strenuous endurance exercise, post-exercise changes in cytokines do occur, but they are generally of a smaller magnitude, and occur at a later time period after the termination of exercise.