SUZUKI, K., S. NAKAJI, M. YAMADA, Q. LIU, S. KURAKAKE, N. OKAMURA, T. KUMAE, T. UMEDA, and K. SUGAWARA. Impact of a Competitive Marathon Race on Systemic Cytokine and Neutrophil Responses. Med. Sci. Sports Exerc., Vol. 35, No. 2, pp. 348–355, 2003. To investigate whether cytokines and neutrophils mediate exercise-related pathogenesis, we examined their responses and possible association after exhaustive exercise. Plasma and urine samples were obtained from 10 male runners before and after a 42.195-km marathon race. Major cytokines and neutrophil activation markers [myeloperoxidase (MPO) and lactoferrin (LTF)] were measured by enzyme-linked immunosorbent assays. Functional modulation of standard neutrophils and monocytes by plasma was determined in vitro on their luminol-dependent chemiluminescence responses. The race induced peripheral neutrophilia accompanied by an increase in band neutrophils and monocytosis. Plasma MPO and LTF concentrations increased significantly by 1.8 and 1.4 times after the race. There was a greater increase in urine concentrations of MPO and LTF, 12.3 and 3.5 times after exercise, respectively, suggesting that neutrophil activation occurred and that renal clearance exceeded the increase in plasma concentrations. Plasma interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), and monocyte chemotactic protein 1 (MCP-1) increased significantly after the race, and urine IL-1, IL-6, G-CSF, M-CSF, and MCP-1 increased significantly. The plasma IL-6 responses correlated with the increases of band neutrophil count (r 0.860, P 0.01), suggesting IL-6-mediated bone marrow release of neutrophils. Furthermore, the increases in urine MPO concentration were correlated with increases in urine IL-6 (r 0.868, P 0.01) and G-CSF (r 0.875, P 0.01), suggesting that these cytokines promoted neutrophil activation in vivo. However, in vitro preincubation of neutrophils and monocytes with postexercise plasma could not cause priming responses, possibly because of the exercise-induced enhancement of plasma antioxidant activity. Although many cytokines recruiting and priming neutrophils and monocytes were secreted and functional after exhaustive exercise, overwhelming antioxidant and antiinflammatory defenses were induced, preventing exercise-induced oxidative stress. Key Words: INFLAMMATION, LEUKOCYTES, CHEMOKINES, ADHESION MOLECULES, FREE RADICALS