Cross-sectional analysis of blood leukocyte responsiveness to interleukin-10 and interleukin-6 across age and physical activity level.

Objectives: To determine how the anti-inflammatory actions of interleukin-10 (IL-10) and IL-6 differ across age and physical activity levels.

Methods: Using a cross-sectional design, fasted blood samples were obtained from younger physically inactive (YI: n=10, age: 22.7 ± 3.7 years, BMI: 24.8 ± 4.8 kg/m², <150 min of weekly moderate-to-vigorous physical activity [MVPA]), younger highly active (YA: n=11 varsity cross country running athletes, 20.7 ± 2.7 years, 21.1 ± 1.8 kg/m², >300 min of weekly MVPA), and older highly active (OA: 12, 56.0 ± 10.3 years, 22.8 ± 3.2 kg/m², >300 min of weekly MVPA) individuals and analyzed for leukocyte counts, IL-10 and IL-6-related signaling, and cytokine secretion ex vivo.

Results: Total white blood cells and monocytes were similar between groups (p=0.8) but YA and OA had lower lymphocyte counts than YI (p<0.01). The ability of IL-10 (1 ng/mL) to phosphorylate signal transducer and activator of transcription 3 (STAT3) in CD14 monocytes was greater in YA vs. YI (p<0.03) despite YA having lower IL-10 receptor expression (p<0.01). IL-6 (10 ng/mL) mediated STAT3 phosphorylation in CD4 lymphocytes was higher in OA compared YI (p<0.01), with a similar tendency observed for YA vs. YI (p=0.08). Despite enhanced responsiveness of STAT3 to IL-10/6 in active individuals, the ability of IL-10/6 to inhibit tumor necrosis factor-alpha (TNF-⍺) secretion from lipopolysaccharide-stimulated whole-blood was similar between groups.

Conclusions: Highly active younger and older individuals demonstrate enhanced IL-10- and IL-6-mediated activation of immune cell STAT3. Although the ability of IL-10/6 to inhibit TNF-⍺ secretion appeared unimpacted by activity level, anti-inflammatory cytokine actions were preserved in older active individuals.