Mild Endotoxaemia and the Inflammatory Response Induced by a Marathon Race

Abstract

1. To address the question of whether endotoxaemia could be involved in the inflammatory response induced by long-term strenuous exercise, 18 male marathon runners [mean age 41 +/- 2 (SEM) years] were studied. Their performance in the marathon ranged from 2 h 46 min to 4 h 42 min. 2. Four venous blood samples were drawn: at rest, just before the race (baseline); within 15 min following the completion of the marathon; after 1 h of recovery; and the morning after the race. 3. The following humoral markers of the inflammatory response to exercise were measured: polymorphonuclear myeloperoxidase (MPO), anaphylatoxin C5a (C5a), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Plasma endotoxin was measured by a sensitive and rapid chromogenic Limulus assay. All inflammatory markers were significantly increased (P < 0.001) after the race, reaching in most cases peak values in the first blood sample drawn following the completion of the marathon [MPO, 298 +/- 19 ng/ml (SEM); C5a, 1.45 +/- 0.32 ng/ml; TNF-alpha, 20 +/- 3 pg/ml; IL-6, 88 +/- 13 pg/ml] when compared with baseline [MPO, 146 +/- 16 ng/ml (SEM); C5a, 0.27 +/- 0.2 ng/ml; TNF-alpha, 12 +/- 1.5 pg/ml: IL-6, 1.0 +/- 0.5 pg/ml]. Traces of plasma endotoxin (ranging from 5 to 13 pg/ml, with one exceptionally high value of 72 pg/ml measured in one runner) were detected in seven subjects within the first hour of recovery. An ELISA method was used to determine the endogenous IgG antibodies toward a range of Gram-negative bacterial lipopolysaccharides (LPSs) of different sizes and structures. A transient decrease in certain anti-LPS activities, mainly against rough LPS, occurred in most cases in the first blood sample drawn after the race. There was no correlation between the magnitude of the inflammatory response to exercise, as assessed by the increase in blood levels of humoral markers of inflammation, and the changes in circulating endotoxin levels of anti-LPS IgG activity following the race. 4. From these results, we conclude that the mild, transient endotoxaemia detected in some of our subjects does not play a major role in the observed inflammatory response to a marathon competition.

Acute hepatic response to diet modification and exercise-induced endotoxemia during a laboratory-based duathlon

“…A very low-CHO diet implies a very high-fat dietary content, which has been shown detrimental to immune function. We expected to find an increase in IL-6 from baseline following exercise in both dietary conditions, as previously reported in measurements taken after light, moderate and hard intensity exercise performed for short-and long-periods of time [2,7,12,22,27,34,40,51]. In our study, IL-6 increased significantly from baseline immediately following the duathlon regardless of the diet, and remained elevated 1-and 2-h following exercise.…”

“…This exercise intensity caused bacterial translocation immediately following exercise similar to that reported in marathon and ultra-endurance events [3,4,6,7,27,44].…”

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

“…Recent analysis using intracellular staining confirmed that CD14 ϩ CD16 ϩ monocytes are major producers of TNF-␣ and possess a higher sensitivity for LPS-induced TNF-␣ production in vivo compared with CD14 ϩϩ CD16 Ϫ monocytes (6,62,64). Therefore, it seems plausible that CD14 ϩ CD16 ϩ monocytes are responding to mild endotoxemia accompanying strenuous exercise (9,50) or EHS (68). A common finding when examining intracellular cytokine profiles with exercise, with or without hyperthermia, has been either no change or a slight reduction in the level of spontaneous TNF-␣ in cytokine-positive peripheral blood monocytes in trained (74,77,89) and untrained subjects (84), similar to the present study's responses in CD14 ϩϩ CD16 Ϫ monocytes.…”

Neutrophil migration during endotoxemia

“…Elevated plasma endotoxin concentration is associated with various activities such as alcohol consumption and with gastrointestinal distress after strenuous exercise or general anesthesia [89,[225][226][227]. In otherwise healthy individuals, stress, pharmaceuticals, toxicants, and dietary alterations together or individually can increase plasma endotoxin by enhancing gut permeability and/or by reducing clearance by liver macrophages [reviewed in 228].…”

“…However, both fibrinogen and factor X bind to PMNs in vitro [221,222]. Furthermore, fibrinogen inhibits PMN chemotaxis in vitro [223], and a peptide derived from factor X can bind to CD11b/CD18 on PMNs and inhibit transendothelial migration [226]. In this scenario, the reduced concentration of fibrinogen in plasma between 2 and 6 h of endotoxemia might free CD11b/CD18 for ICAM-1 binding and thereby promote adhesion and migration.…”