Circulating levels of cytokines (IL-6 and IL-1beta) in patients with intermittent claudication, at rest, after maximal exercise treadmill test and during restore phase. Could they be progression markers of the disease?

Aim: Inflammation is considered to be one of the main mechanisms for the development and progression of peripheral arterial disease (PAD). Many studies have demonstrated that maximal exercise enhances the acute inflammatory response in claudicant patients, but no one has assessed the duration of this acute inflammatory activation. The aim of this study was to assess of the inflammatory pattern in claudicants and of the inflammatory response after maximal exercise and during the recovery from calf pain.

Methods: Eleven patients with moderate claudication (MC) (age: 60.5+/-5.8 years; body mass index [BMI]: 27.5+/-4.6; absolute claudication distance [ACD]: 165.4+/-38), 10 patients with severe claudication (SC) (age: 60.3+/-5 years; BMI: 27+/-4.5; ACD: 91+/-11.3) and 8 healthy subjects (age: 59.4+/-6.8; BMI: 28.7+/-4.16) underwent to maximal treadmill test (speed 2.5 km/h, slope 15%). At rest, just after stop of the exercise (appearance of calf pain in patients, and 6 min of treadmill in controls) the circulating levels of interleukin (IL)-1beta and IL-6 have been measured.

Statistical Analysis: variance of mean values, Bonferroni t-test, split plot variance model, variance of d stop-before and stop-recovery have been utilized. P<0.05 has been considered the significant cut-off of the differences.

Results: The maximal exercise excited significant (P<0.01) inflammatory activation in all patients: MC (rest IL-1beta: 1.55, 3.3 at stop; rest IL-6: 5.97, 8.38 at the stop); SC (rest IL-1beta: 2.97, 5.72 at stop; rest IL-6: 6.98, 9.99 at the stop). During recovery, MC showed a reduction of the inflammatory activation, whilst SC showed further increase (IL-1beta: 7.55; IL-6: 11.94).

Conclusion: The study confirms the higher inflammatory activation in claudicants and its enhancement after maximal exercise. During recovery, we found two kinds of response: type 1 (controls and MC), in which inflammation subsides, and type 2 (SC) characterized by further inflammatory increase. This trend is not univocal: 3 MC showed a type 2 response and 2 SC showed a type 1. In conclusion, inflammatory activation may depend not only on the degree of endothelial damage, but also on the individual inflammatory attitude, better assessed after maximal exercise than baseline values. This individual inflammatory responsiveness, considering the role of the rest measurement of markers of inflammation recently discussed, could be a useful marker for aggressive PAD.