Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients

Abstract

The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=-0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the antiinflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients.

Expression of IL-10 and TNF-α in Rats with Cerebral Infarction after Transplantation with Mesenchymal Stem Cells

“…These effects of IL-10 were thought to contribute to infarct volume reduction and neurological improvement after experimental focal cerebral ischemia (19)(20)(21)(22). It also reported previously that in IL-10 knockout in rats for a MCAO could augment neurological deficits and increase infarction volume (23). Recent animal experiments demonstrated that MSCs transplantation alone improved neurological deficits in cerebral infarction.…”

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

“…During the stroke pathophysiological processes, an alteration of anti-inflammatory molecules has been also described in humans. More in detail, IL-1RA and TGF-b are over expressed after ischemic stroke, 66,67 whereas circulating IL-10 have been found to be lower in patients than in controls 68 and have been associated with more extensive pathology. 69 Thus, it is well-established that cytokine network plays an important role in the initiation and maintenance of damage-related inflammation in patients suffering from stroke.…”

“…Moreover, the fact that IL-18 seems to mediate delayed neuroinflammatory events after hypoxic-ischemic brain injury, 101 makes this cytokine particularly interesting in the design of a tentative correlation between temporal expression in the brain of stroke-induced cytokines and the activation of poststroke biological mechanisms leading to depression. In this respect, the observation that during the pathophysiological process of stroke, anti-inflammatory cytokines are produced at a later time 68 than inflammatory cytokines, provides a rational for further studies aimed to clarify differences in early versus delayed onset poststroke depression pathogenesis. Eventually, the cytokine hypothesis may provide a missing link to explain why poststroke depression leads to impaired physical and cognitive recovery and increased mortality.…”

Immuno-inflammatory and thrombotic/fibrinolytic variables associated with acute ischemic stroke diagnosis

“…We chose to evaluate these biomarkers because acute ischemic stroke has been associated with serum elevations of a series of immuno-inflammatory variables such as TNF-␣, interleukin-6 (IL-6) and other cytokines, selectins and adhesion molecules [7][8][9][10] and of markers of impaired hemostasis and thrombosis [11][12][13].…”