Initially, it was thought that the cytokine response to exercise represented a reaction to exercise-induced muscle injury or transposition of lipopolysacharide (LPS) to the gut. However, recent data suggest that the massive response of IL-6 to exercise may primarily mediate important exercise-related metabolic changes [4,5]. Several cytokines can be detected in plasma during and after strenuous exercise [6-8]. Most studies report that exercise does not induce an increase in plasma levels of TNF-a except a few studies demonstrating that strenuous, prolonged exercise, such as marathon running results in a small increase in the plasma concentration of TNF-a . Thereby, the cytokine cascade due to exercise differs from the cytokine response to infec tions. The first cytokine that is present in the circulation following exercise is IL-6, which may increase 100 fold. The increase in IL-6 is followed by a marked increase in the concentration of IL-lra [4,6]. The cytokine inhibitors (IL-lra and sTNF-R) as well as the anti-inflammatory cytokine IL-10  increase, and also the concentrations of the chemokines, IL-8, MIP-1 alpha and MIP-1 beta, are elevated after a marathon race [11,12]. Interleukin 8 (IL-8) is produced by various cells upon stimulation and influences a variety of functions of leukocytes in particular neutrophils. Systemic administration of IL-8 induces a rapid neutropenia associated with sequestration of neutrophils in the lung which is followed by a neutrophilia characterised by the rapid release of neutrophils from the bone marrow. These cells are released predominantly from the bone marrow venous sinusoids . Increased levels of plasma-chemokines in response to exercise have only been described if the exercise has been extremely exhaustive suggest as in a marathon [11,12], whereas even 2.5 hours of treadmill running did not cause an increase in plasma-chemokines . Thus, it is not known if chemokines are involved in post-exercise neutrophilia.
When blood mononuclear cells are sampled during or following strenuous exercise and stimulated in vitro to produce cytokines, it has been reported that the in vitro cytokine production is either impaired [14,15], not changed or enhanced . These findings are likely to be explained by exercise-induced altered blood mononuclear cell composition.
In addition to cytokines, serum levels of non-cytokine acute phase reactants, including serum amyloid A inducer (SAA), C-reactive protein (CRP), serum amyloid A, haptoglobulin, cerulo-plasmin, transferrin and a macroglobulin, also change with inflammation . Many of these acute phase reactants have essential roles in host defence; for example, ceruloplasmin and transferrin may have antioxidant functions . With respect to exercise models, the serum levels of these acute reactants have not been well characterised with the exception of transferrin.
The concentration of serum transferrin, a (3 ^globulin carrier protein of iron which is synthe-sised in the liver, decreases with inflammation and trauma . Transferrin may play a role in nonspecific host defence against bacterial pathogens through the 'iron binding' hypothesis . However, when samples were corrected for plasma volume shifts, transferrin concentrations did not change immediately after, 30, 60 or 120 minutes after high intensity swimming or treadmill exercise in athletes . In contrast, blood concentration of a related acute phase iron transport molecule, ferritin, was significantly decreased at 5 and 7 days post exercise compared with immediately and 1 day post exercise . Iron-binding capacity and percentage of saturation of transferrin did not change after 12 weeks of moderate endurance walking/running or cycling exercise in 31 women . In rangers participating in an eight week USA training course, and who had associated energy deficit of about 1000 kcal/d, there were no effects on serum transferrin concentrations , In contrast, transferrin concentration decreased significantly in male recruits undergoing prolonged physical stress during survival training , It is not possible, however, to disentangle the effects of the physical exercise from restricted water and food intake on the levels of serum transferrin that were observed in this study. C-reactive protein (CRP) concentration was unchanged after either uphill running or 24 hours after downhill running , However, CRP levels increased in elderly subjects following an intensive training programme ,
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