Effects of very early exercise on inflammatory markers and clinical outcomes in patients with ischaemic stroke- a randomized controlled trial

Background: Apart from the limited evidence of the effects of very early exercise (VEE) on clinical outcomes (COs) in stroke, better knowledge is required to understand the cellular action induced by VEE. This study investigated the effects of VEE on inflammatory markers (IMs) and COs. It further evaluated the association between acute changes in IMs and COs at follow-up in individuals with first-ever mild-to-moderate ischaemic stroke. Methods: A prospective, single-center, single-blind, randomized controlled trial (retrospectively registered: PACTR202406755848901; 10–06-2024) was conducted. Forty-eight patients randomized (1:1) into the VEE group (VEEG) and usual care group (UCG) completed the follow-up. Within 24 h of stroke onset, patients in VEEG underwent 45 min of VEE twice daily, amounting to 1.5 h/d, for seven days while patients in UCG received regular turning and positioning. The levels of IMs including interleukin-6 (IL-6), fibrinogen, leucocytes, neutrophils, lymphocytes, and monocytes were assessed at baseline, 4th, and 7th day for both groups. Thereafter, each patient received 90-min follow-up physiotherapy twice weekly for three months. Motor impairment, physical disability, functional independence, anxiety, depression, and cognition were evaluated at 1st and 3rd month of follow-up. Results: On the 4th and 7th day, patients in VEEG show trends of lower levels of IL-6, leucocytes, neutrophils, and monocytes and higher levels of lymphocytes. However, a non-linear effect of VEE on plasma fibrinogen was observed compared to UC. Furthermore, better improvement in motor impairment, physical disability, functional independence, anxiety, depression, and cognition were observed in VEEG. The positive modulation of IMs by VEE was associated with COs over time, including associations between changes in IL-6 at days 4 and 7 and 3-month functional independence (rs = -0.33; p = 0.019; rs = -0.33; p = 0.021), and at day 7 and 3-month motor impairment (rs = 0.30; p = 0.039). Conclusions: Initiating moderate-intensity exercise within 24 h appears beneficial in positively modulating IMs, including IL-6, at the acute stage and improving the physical, motor, cognitive, and affective functions at 1-and 3-month follow-up. The association between exercise-induced acute changes in IMs and improved COs over time highlights the potential role of moderate-intensity VEE in enhancing stroke recovery through positive inflammatory modulation. © The Author(s) 2025.