Impact of training status on LPS-induced acute inflammation in humans

Abstract

The aim of the present study was to examine the impact of training status on the ability to induce a lipopolysaccharide (LPS)-induced inflammatory response systemically as well as in skeletal muscle (SkM) and adipose tissue (AT) in human subjects. Seventeen young (23.8 ± 2.5 yr of age) healthy male subjects were included in the study with eight subjects assigned to a trained (T) group and nine subjects assigned to an untrained (UT) group. On the experimental day, catheters were inserted in the femoral artery and vein of one leg for blood sampling and a bolus of 0.3 ng LPS/kg body wt was injected into an antecubital vein in the forearm. Femoral arterial blood flow was measured by ultrasound Doppler, and arterial and venous blood samples were drawn before (Pre) LPS injection and 30, 60, 90, and 120 min after the LPS injection. Vastus lateralis muscle and abdominal subcutaneous AT biopsies were obtained Pre and 60 and 120 min after the LPS injection. LPS increased the systemic plasma TNFα and IL-6 level as well as the TNFα and IL-6 mRNA content in SkM and AT of both UT and T. However, whereas the LPS-induced inflammatory response in SkM was enhanced in T subjects relative to UT, the inflammatory response systemically and in AT was somewhat delayed in T subjects relative to UT. The present findings highlight that training status affects the ability to induce a LPS-induced acute inflammatory response in a tissue-specific manner.

Habitual physical activity protects against lipopolysaccharide-induced inflammation in mouse adipose tissue

“…6 In a crosssectional study design, Olesen et al 6 observed an increase in IL-6 mRNA expression in response to LPS in subcutaneous adipose tissue of trained subjects, an effect that was not recapitulated, albeit in mice, in the current investigation. Although the results of our study and that of Olesen et al 6 are divergent, it is difficult to directly compare this study to ours due to differences in species examined.…”

“…6 In a crosssectional study design, Olesen et al 6 observed an increase in IL-6 mRNA expression in response to LPS in subcutaneous adipose tissue of trained subjects, an effect that was not recapitulated, albeit in mice, in the current investigation. Although the results of our study and that of Olesen et al 6 are divergent, it is difficult to directly compare this study to ours due to differences in species examined. 37 Further, we used a significantly larger dose of LPS (2 mg/kg vs 0.3 ng/kg), which at least in mice is known to induce near peak inflammation, 23 and the time of assessment post-LPS treatment was also slightly different between studies.…”

“…6 In subcutaneous adipose tissue from exercise trained individuals, the induction of inducible nitric oxide synthase (iNOS) and TLR4 mRNA expression was decreased, while the induction of IL-6 mRNA expression was increased, and TNF-a mRNA expression was unaltered. 6 While this study did not directly assess the protective effects of exercise training per se, the results indicate that training status may alter the response of adipose tissue to LPS-induced inflammation. As this dose of LPS does not elicit a peak inflammatory response, but is required for tolerability in humans, it is possible that a greater protective effect of physical activity or exercise against higher doses of LPS may be found.…”

“…4,5 This systemic pro-inflammatory environment induces increases in inflammation at the organ level, including in adipose tissue. 6 As adipose tissue is a key contributor in the inflammatory response to numerous metabolic stimuli, 7 it is important to understand the etiology of sepsis-induced inflammation in adipose tissue and if there are potential preventative strategies.…”

Aerobic Exercise Training and Inducible Inflammation: Results of a Randomized Controlled Trial in Healthy, Young Adults

“…In vivo administration of lipopolysaccharide to healthy, young, trained or untrained men revealed tissue‐specific induced inflammatory responses: Compared with their untrained counterparts, trained subjects had an enhanced lipopolysaccharide‐induced TNF‐α and IL‐6 mRNA expression in skeletal muscle and slightly reduced responses systemically and in adipose tissue 37. Some animal studies also report increases in ex vivo lipopolysaccharide‐stimulation models, with exercise training leading to increases in TNF‐α but not IL‐6 in rats38, 39 in interleukin‐1ß, interleukin‐12, TNF‐α, and interferon‐γ in mice,40, 41, 42, 43 and in TNF‐α and interferon‐ß in horses 44…”