Change of walking distance in intermittent claudication: impact on inflammation, oxidative stress and mononuclear...

Atherosclerosis is a chronic inflammatory process involving the immune system and formation of reactive oxygen species (ROS). We investigated changes of mononuclear blood cells and ROS production in relation to the walking distance of patients with intermittent claudication during home-based exercise training.

Forty patients with intermittent claudication were asked to perform a home-based exercise training for a mean time of 12 months. ROS formation was measured using the luminol analogue L-012. Peripheral blood leucocytes [monocytes, polymorphonuclear neutrophils (PMN) and dendritic cells (DC)] were analysed by flow cytometry and analysed for the expression of major inflammatory surface molecules.

At follow-up, patients showed an increased walking distance and reduced ROS production upon stimulation with a phorbol ester derivative (PDBu) (p < 0.01). Monocytes changed their inflammatory phenotype towards an increased anti-inflammatory CD14(++)CD16(-) subpopulation (p < 0.0001). Adhesion molecules CD11b, CD11c and TREM-1 on monocytes and PMN decreased (all p < 0.01). On DC expression of HLA-DR, CD86 or CD40 decreased at follow-up. Inflammatory markers like fibrinogen, C-reactive protein or soluble TREM-1 (sTREM-1) decreased over the observation period. Finally, we found a close relation of sTREM-1 with the walking distance, fibrinogen and ROS production.

We observed an amelioration of the proinflammatory phenotype on monocytes, DC and PMN, as well as a reduced ROS production in PAD patients under home-based exercise, paralleled by an increased walking distance. Our data suggest that a reduced inflammatory state might be achieved by regular walking exercise, possibly in a dimension proportionately to changes in walking distance.