Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity‐dependent reductions in anti‐inflammatory cytokine action
Bibliographic record
Abstract
Abstract Circulating interleukin (IL)‐6 and IL‐10 concentrations are widely used to evaluate the anti‐inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti‐inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL‐6 and IL‐10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30 ± 3 years; body mass index: 22.8 ± 2.3 kg/m 2 ; : 51 ± 6 mL/kg/min) completed a no‐exercise control condition (CTL) or isocaloric bouts of cycling performed below (moderate continuous exercise; MCE) or above (heavy continuous or heavy intermittent exercise; HCE or HIE, respectively) lactate threshold. Venous blood (before, after, 30 min after and 90 min after exercise) was analysed for immune cell subpopulations, plasma cytokine concentrations, anti‐inflammatory cytokine action and monocyte phenotype. Exercise induced rapid leukocytosis ( P < 0.001) and increased plasma IL‐6 ( P < 0.001), IL‐10 ( P = 0.0145) and tumour necrosis factor‐⍺ (TNF‐⍺) ( P = 0.0338) concentrations in an intensity‐dependent manner (HCE and/or HIE vs . CTL). These systemic changes coincided with a diminished ability of IL‐10/6 to phosphorylate STAT3 ( P < 0.001) and inhibit TNF‐⍺ secretion ( P = 0.0238) in blood leukocytes following HCE and HIE. Monocyte polarization experiments revealed lower CD80 [MCE ( P = 0.0933) and HIE ( P = 0.0187) vs . CTL] and a tendency for higher CD163 expression (HCE vs . CTL, P = 0.0985), suggesting that hyporesponsiveness to anti‐inflammatory cytokine action does not impede the ability of exercise to promote an anti‐inflammatory monocyte phenotype. These findings provide novel insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti‐inflammatory effects of exercise. image Key points Circulating cytokine concentrations are frequently used to evaluate the anti‐inflammatory effects of exercise but may not capture changes in cytokine action occurring at the cellular level. We directly assessed anti‐inflammatory cytokine action – measured using a combination of intracellular signalling and cytokine secretion ex vivo – in distinct immune cell subpopulations after acute calorie‐matched exercise bouts differing in intensity and pattern. Anti‐inflammatory cytokine action was blunted following higher intensity exercise despite corresponding increases in circulating cytokine concentrations and immune cell counts. Changes in cytokine action were not explained by changes in cytokine receptor expression on circulating immune cells. Our findings provide new insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti‐inflammatory effects of exercise.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".