It has been suggested that exercise intensity is of importance in the regulation of increase in pro-inflammatory molecules, but there is still a debate about the effect of duration on these molecules. Therefore, the effect of exercise duration on the serum concentrations of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), soluble form of intercellular adhesion molecule-1 (sICAM-1), and matrix metalloproteinase-9 (MMP-9) was studied in 22 half-marathon (HM) and 18 marathon (M) male amateur runners who completed their exercise task in 1.8 ± 0.2 (mean ± standard deviation) and 3.6 ± 0.4 h, respectively (thus, average speed was 11.7 ± 1.5 and 11.9 ± 1.8 km h(-1), respectively). Blood was sampled 2 days before, 15 min after, and 28 h after the race. IL-6, TNF-α, and MMP-9 always increased immediately after exercise, but the increase was larger (P < 0.05) in M versus HM (∆IL-6: 31 ± 24 vs. 5 ± 4 pg ml(-1); ∆TNF-α: 1.7 ± 1.9 vs. 0.5 ± 0.8 pg ml(-1); MMP-9: 288 ± 216 vs. 145 ± 128 ng ml(-1), respectively). sICAM-1 also increased with exercise, but similarly in M and HM (20 ± 40 vs. 23 ± 32 ng ml(-1), respectively). Only sICAM-1 remained elevated 28 h post-exercise in both HM and M, while IL-6, TNF-α, and MMP-9 returned to pre-exercise levels. Competitive HM and M races induce significant increases in IL-6, TNF-α, sICAM-1, and MMP-9 concentrations. As HM and M runners performed the competition with similar absolute intensity, the difference in response between the groups suggests that exercise duration is of importance in the regulation of IL-6, TNF-α, and MMP-9, but not sICAM-1 concentrations in response to prolonged running.

Interleukin-6 (IL-6) is a multifunctional cytokine that exerts its modulatory effects on cells that express membrane bound IL-6 receptors; however, IL-6 in a complex with soluble IL-6R can bind to any cell that express glycoprotein 130 (gp130). Thus, all cell types may respond to the pro- as well as anti-inflammatory properties of IL-6. Since the first report of acute exercise-induced increase in plasma IL-6 in the early 1990s, scientists have tried to elucidate the factors that influence the magnitude of change of plasma IL-6, as well as the possible biological roles of this cytokine. Evidence suggests that exercise intensity and duration as well as the form of contraction (e.g., eccentric or concentric) and muscle damage all influence IL-6 response to acute exercise. However, data on training status and performance on plasma IL-6 concentration changes during exercise are more inconclusive, as discussed in this review. In the last decade, most of the studies have focused on IL-6 as an 'energy sensor' possibly secreted by skeletal muscle that activates glycogenolysis in the liver and lipolysis in fat tissue in order to provide muscle with the growing energy demands during exercise.

The aim of this study was to test the hypothesis that exercise would induce inflammatory response characterized by increased pro‐inflammatory cytokines – interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α), adhesion molecule, matrix metalloprotease‐9 (MMP‐9) and myeloperoxidase (MPO) levels. Additional aim was to elucidate the possible source of maximal exercise‐induced increase in MMP‐9 concentration. To examine our hypothesis, 26 professional male ice hockey players [age 25 ± 1 (mean ± SEM) years; BMI 25.8 ± 0.4 kg/m2] performed an incremental bicycle test until exhaustion, when maximal oxygen consumption was recorded. Venous blood samples were collected 30 min before and 2 min after exercise. There was an increase in the count of leucocytes (8.7 ± 1.8 versus 5.7 ± 1.3 × 109 cells per l) and IL‐6 (1.24 ± 0.17 versus 0.69 ± 0.13 pg/ml), MPO (72 ± 7 versus 50 ± 4 ng/ml) and MPP‐9 (139 ± 9 versus 110 ± 6 ng/ml) concentrations (P < 0.05) comparing post‐ and pre‐exercise levels. Maximal exercise‐induced increase in MPO correlated with the increases in IL‐6 (P < 0.05, R = 0.54) and MMP‐9 (P < 0.01, R = 0.62) concentrations. Furthermore, increase in IL‐6 correlated with the increase in MMP‐9 concentrations (P < 0.05, R = 0.60). Maximal exercise induces an inflammatory response characterized by leucocytosis and increased IL‐6, MPO and MMP‐9 concentrations. Correlations between increased MPO (marker of neutrophils degranulation) and both increased IL‐6 and MMP‐9 concentrations may suggest that neutrophils could be the main source of these inflammatory biomarkers during maximal exercise. Furthermore, correlation between increases in serum IL‐6 and MMP‐9 concentrations may suggest that IL‐6 could exert modulatory effects on MMP‐9 release during maximal exercise.