Regular Training Increases sTWEAK and Its Decoy Receptor sCD163–Does Training Trigger the sTWEAK/sCD163-Axis to Induce an Anti-Inflammatory Effect?

Abstract

Background: Low levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were reported in patients with coronary artery disease, heart failure, chronic kidney disease and diabetes mellitus. Soluble cluster differentiation 163 (sCD163) serum levels are related to M2 macrophages, having anti-inflammatory attributes. As sport is well-known for its anti-inflammatory and cardioprotective effects we aimed to investigate the influence of eight months of physical activity on serum sCD163 and sTWEAK levels. Methods: In total, 109 subjects with at least one cardiovascular risk factor were asked to perform endurance training within the calculated training pulse for eight months. Overall, 98 finished the study. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. The cohort was divided into four groups, dependent on their baseline performance and performance gain. sCD163 and sTWEAK were measured at baseline and after two, six and eight months by ELISA. Results: Those participants who had a performance gain of ≤2.9% (mean gain 12%) within eight months showed a significant increase in sTWEAK (group 2: from 133 to 200 pg/mL, p = 0.002 and group 4: from 166 to 212 pg/mL, p = 0.031) and sCD163 levels (group 2: from 255 to 348 ng/mL, p = 0.035 and group 4: from 247 to 288 ng/mL, p = 0.025) in contrast to subjects without performance gain (sTWEAK: group 1: from 161 to 177 pg/mL, p = 0.953 and group 3: from 153 to 176 pg/mL, p = 0.744; sCD163: group 1: from 289 to 256 ng/mL, p = 0.374 and group 4: from 291 to 271 ng/mL, p = 0.913). Baseline sCD163 correlated with erythrocyte count, hematocrit, ASAT and lipoprotein a, the presence of hypertension and a BMI > 30 kg/m2. Conclusion: Regular physical activity leads to a significant increase in sCD163 and sTWEAK levels of up to 37% and 50%, respectively. It is well-known that physical activity prevents or retards the onset and genesis of chronic inflammatory disease. One possible way of how training evolves its beneficial effect might be by modifying the inflammation status using the sTWEAK–sCD163 axis. Brief Summary: Regular physical activity leads to a significant increase in sTWEAK and sCD163 levels. Both factors are diminished in patients with chronic (inflammation-based) diseases, such as coronary artery disease, heart failure, pulmonary artery hypertension, chronic kidney disease and diabetes mellitus. It seems that the amounts of soluble TWEAK and CD163 are essential for a healthy balance and modulation between pro- and anti-inflammatory processes, and regular physical training could use the sCD163–sTWEAK axis to unfold its beneficial effect.

Targeting of CD163+ Macrophages in Inflammatory and Malignant Diseases

“…Further, a recent paper reviewed sCD163 as a potential biomarker of acute and chronic liver disease and found it elevated in relation to severity in multiple studies [ 91 ]. Long-term physical activity also increases sCD163 levels which may be owing to a counteracting effect of CD163 + macrophages on exercise-induced pro-inflammatory effects [ 92 ]. sCD163 has also been used as a biomarker in other tissue fluids than serum/plasma.…”

Beyond the Finish Line: The Impact and Dynamics of Biomarkers in Physical Exercise—A Narrative Review

“…Regular physical activity causes a slight increase in both TWEAK and sCD163 levels, therefore maintaining an equilibrium between pro- and anti-inflammatory markers [ 81 , 82 ]. In this regard, literature data emphasizes that mild, temporary activation of the TWEAK-FN14 axis by regular physical activity is a physiological and promyogenic phenomenon, while a persistent chronic axis activation (due to injuries or hyperinflammation) induces increased proteolysis, thus causing subsequent muscular atrophy and sports underperformance [ 77 , 83 ].…”

RANTES and CD40L under Conditions of Long-Term Physical Exercise: A Potential Link to Adaptive Immunity

“…The influence of increased physical activity on inflammation and lipid metabolism biomarkers such as sTWEAK/sCD163, sRAGE, and adipsin/ANGPTL4 has already been investigated by our group [ 24 , 25 , 26 ]. In the present study, we aimed to illuminate the effect of long-term exercise on RANTES and CD40L.…”