To investigate the time course of leukocyte accumulation in eccentric exercised human muscles and its relation to recovery of muscle function and soreness. Eleven young males performed 300 unilateral, maximal voluntary, eccentric actions with the musculus quadriceps femoris (30 degrees x s(-1)). Before and at regular intervals for 7 d after exercise, force-generating capacity was measured with maximal concentric knee extensions (60 degrees x s(-1)). Accumulation of radiolabeled (autologous) leukocytes was measured with scintigraphy. Biopsies from musculus vastus lateralis were obtained 0.5, 4, 8, 24, 96, and 168 h after exercise from both the exercised leg and the control leg. Muscle cross-sections were stained with antibodies against leukocytes (CD16 and CD68). Muscle soreness was rated on a visual analog scale. Immediately after exercise, the subjects' ability to generate force was reduced by 47 +/- 5%. Muscle function recovered slowly and was not fully restored after 1 wk. Radiolabeled leukocytes accumulated in the muscles during the first hour (3-24 h) after exercise, and leukocytes were at the same time observed histologically, primarily in the endomysium and perimysium. A part of the accumulated radiolabeled leukocytes appeared to be located within local blood vessels. The highest numbers of CD16(+) and CD68(+) cells were found 4 and 7 d after exercise. There was a positive correlation between accumulation of radiolabeled leukocytes and muscle weakness measured 1-3 d after exercise (r = 0.8, P < 0.05) and, surprisingly, a negative correlation between radiolabeled leukocyte accumulation and muscle soreness (r = -0.96, P < 0.01). Exercise-induced muscle damage initiated a rapid local inflammatory response that gradually increased over the next days. Halted recovery of muscle function was associated with local accumulation of leukocytes, whereas muscle soreness could not be explained by the presence of leukocytes.

Delayed leukocytosis after strenuous exercise is well documented, but the underlying mechanisms are not clear. In this study, we investigated the relationship between exercise-induced muscle damage and delayed leukocytosis, by utilizing an extreme eccentric exercise protocol. We obtained blood samples from 11 healthy men before and after 300 maximal eccentric actions with m. quadriceps. Maximal force-generating capacity was tested before and regularly during the 7 d after exercise. Blood was analyzed for leukocytes, growth hormone (GH), cortisol, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1beta (MIP-1beta), creatine kinase (CK), C-reactive protein (CRP), complement activation products (C3bc and the terminal complement complex (TCC)), and chemotactic activity in plasma. The force-generating capacity was reduced by 47 +/- 5% (mean +/- SEM) immediately after exercise. Blood concentration of neutrophils and monocytes and the plasma concentration of G-CSF, IL-6, and MCP-1 peaked 6 h after exercise, whereas M-CSF peaked immediately after exercise. Serum concentration of GH and cortisol also peaked immediately after exercise, whereas the serum concentration of CRP and CK peaked after 2 and 4 d, respectively. At 1 h after exercise, chemotactic activity in plasma was increased; at the same time, concentration of C3bc and TCC were decreased. A positive correlation was found between the acute loss of force and the delayed leukocytosis (r = 0.66; P < 0.05), between peak G-CSF and the delayed neutrophilia (r = 0.65, P < 0.05), between acute loss of force and changes in CK (r = 0.65, P < 0.05), between acute loss of force and changes in CRP (r = 0.65, P < 0.05), and between changes in GH and monocyte blood concentrations (r = 0.68, P < 0.05). The degree of exercise-induced muscle damage seems to be reflected by the magnitude of the subsequent delayed leukocytosis. The signal between the exercised muscle and bone marrow must be investigated further, but G-CSF and GH are putative mobilizing factors.

During infections, polymorphonuclear neutrophilic granulocytes (PMN) are mobilized from their bone marrow stores, travel with blood to the affected tissue, and kill invading microbes there. The signal(s) from the inflammatory site to the marrow are unknown, even though a number of humoral factors that can mobilize PMN, are well known. We have employed a standardized, non-infectious human model to elucidate relevant PMN mobilizers. Well-trained athletes performed a 60-min strenuous strength workout of leg muscles. Blood samples were drawn before, during and just after exercise, and then repeatedly during the following day. Cortisol, GH, ACTH, complement factors, high-sensitive CRP (muCRP), IL-6, G-CSF, IL-8 (CXCL8) and MIP-1β (CCL4) were measured in blood samples. PMN chemotaxins in test plasma was assessed with a micropore membrane technique. About 5 hr after the workout, blood granulocytosis peaked to about 150% of baseline. Plasma levels of GH increased significantly 30 min into and 5 min after the exercise, but no increase was recorded for the other hormones. No significant correlation was found between concentrations of stress hormones and the subjects' later occurring PMN increases above their individual baselines. Plasma G-CSF increased significantly – but within the normal range – 65 min after the workout. IL-6 increased very slightly within the normal range, and the chemokines IL-8 and MIP-1β did not increase consistently. However, we found a significant increase of hitherto non-identified PMN-chemotactic activity in plasma 35, 50, and 60 min after the exercise. No systemic complement activation was detected, and (mu)CRP was within the reference range at rest, 5 h and 23 h after the exercise. After endurance exercise, similar findings were made, except for a cortisol response, especially from non-elite runners. Apparently, a multitude of humoral factors can – directly or indirectly – mobilize PMN from marrow to blood; some of the factors are, others are not known to be, chemotactic. Under different conditions, different selections of these mobilizers may be used. In the late granulocytosis after heavy, long-lasting exercise a number of factors thought capable of mimicking the granulocytosis of infectious diseases were apparently irrelevant.