Immune Cell Mitochondrial Respiration and Inflammatory Profiles Are Partially Modulated by Cardiorespiratory Fitness in Male Adults

Cardiorespiratory fitness (CRF) appears to be related to the metabolic and inflammatory profile of immune cells, though this association is still uncertain. This study presents two main objectives: 1) To determine whether individuals with low-CRF, compared to high-CRF, would have lower peripheral blood mononuclear cells (PBMCs) mitochondrial respiration and higher inflammatory profile, and 2) To analyze the association between PBMCs mitochondrial respiration and cytokine release at rest and upon stimulation. Adults self-reporting male sex were classified as Low- (n = 9) or High-CRF (n = 7) based on established thresholds. To control for confounders, variables related to metabolism, inflammation, body composition, physical activity, and diet were assessed. PBMCs were isolated to evaluate mitochondrial respiration and cytokine release under basal and stimulated conditions (LPS or PMA+ionomycin - in vitro culture during 24h). As main results, PBMCs from individuals with high CRF exhibited higher mitochondrial oxygen consumption than those from the Low-CRF group; however, this difference did not remain after controlling for visceral fat. At rest, PBMCs from low-CRF individuals released more pro-inflammatory cytokines, which correlated negatively with mitochondrial oxygen consumption. Moreover, PBMCs from low-CRF individuals showed strong responsiveness to LPS (higher TNF-α release), while PBMCs from high-CRF individuals showed strong responsiveness to PMA plus ionomycin (higher IFN-γ release), without correlation to mitochondrial respiration. These findings indicate that low CRF is associated with lower mitochondrial respiration and greater basal and LPS-induced cytokine release in PBMCs. Differences in visceral fat appear to be an additional factor associated with PBMCs metabolism and function when comparing individuals with low and high CRF.