Exhaustive Exercise Reduces Tumor Necrosis Factor-α Production in Response to Lipopolysaccharide in Mice

Abstract

Objective: Stressful exercise reduces the plasma pro-inflammatory cytokine concentration in response to lipopolysaccharide (LPS). The aim of this study was to clarify the mechanism of exhaustive exercise-induced suppression of the plasma tumor necrosis factor (TNF)-α concentration in response to LPS. Methods: Male C3H/HeN mice (n = 66) were randomized to treadmill running to exhaustion (Ex) or a sedentary (Non-Ex) condition. Monocytes and splenic macrophages were collected from some animals, and other animals were injected with LPS (1 mg/kg) immediately after the exercise. The liver, lung and spleen tissues in the mice were removed 30 min after the LPS injection for determination of TNF-α mRNA expression. Blood and tissue samples were collected for determination of TNF-α and TNF receptors (TNFR) 1 h after the LPS injection. Results: Although there was a significant suppression in LPS-induced plasma TNF-α in the Ex mice when compared to the Non-Ex mice (p < 0.01), soluble TNFR in plasma was not affected by the exercise. There was no change in cell-surface expression of Toll-like receptor 4 (TLR4) and in LPS-induced TNF-α mRNA expression and TNFR content in tissues between the Ex and Non-Ex groups. Interestingly, TNF-α contents in the liver, lung and spleen of the Ex mice were significantly lower than those of the Non-Ex group (p < 0.01, p < 0.01 and p < 0.05, respectively). Conclusion: These data suggest that exhaustive exercise-induced suppression of the plasma TNF-α concentration despite LPS stimulation might depend on translation of TNF-α in tissues.

The suppression of tumor necrosis factor-alpha production in response to pathogen stimulation by strenuous exercise and underlying mechanisms

“…6). This phenomenon, that pathogen-induced increases in plasma TNF-α concentrations are attenuated by prior exhaustive exercise, seems to be similar to that of LPS-induced TNF-α responses in plasma 35,36,60) . Therefore, intense exercise inhibits poly I:C, R-848 and CpG DNAinduced pro-inflammatory cytokine production, which might increase the risk of infection with viruses (Fig.…”

“…Although Colbert et al 59) reported that exercise-induced changes in the plasma cytokine concentrations are not dependent on tissue (liver, lung and muscle) mRNA expression in mice, they did not find any impact of pathogens, such as LPS, on exercise-induced cytokine production. Recently, Tanaka et al 60) reported that the cell-surface expression of TLR4 on macrophages is unchanged by exhaustive exercise (Fig. 4a).…”

“…Although LPS primarily binds to TLR4/CD14 cells, such as macrophages, and expresses TNF-α mRNA via NF-κB activation 57) , TNF-α mRNA expression, in response to LPS in the liver, lungs and spleen, is not decreased by exhaustive exercise (Fig. 4b) 60) . Clearly, suppression of the plasma and tissue levels of TNF-α in response to LPS does not result from the TNF-α mRNA expression in any of these tissues.…”

Interferon-beta, but not tumor necrosis factor-alpha, production in response to poly I:C is maintained despite exhaustive exercise in mice

“…One group contained exhaustive exercising mice (EX, n = 12), and the other group contained non-exercising mice (N-EX, n = 11). The EX mice were run on a treadmill to exhaustion, and N-EX mice were kept at rest [4,7]. Mean time to exhaustion for EX mice was 65 ± 2 min.…”

“…In fact, we and other researchers have found that high concentrations of proinflammatory cytokines, for example tumor necrosis factor (TNF)-a, in plasma were strongly inhibited by exhaustive exercise before challenge of rodents with lipopolysaccharide (LPS), a gram-negative bacteria component [2][3][4]. In addition, it has been reported that exercise stress might be associated with increased susceptibility to viral infections [5,6].…”