Stroke is a major cause of hospitalization, chronic disability, and death. There is increasing evidence that ischemic brain injury secondary to arterial occlusion is characterized by acute local inflammation. During reperfusion after acute ischemia, polymorphonuclear neutrophils are believed to exacerbate tissue damage by both physical obstruction of vessels and release of oxygen radicals; proinflammatory cytokines, including interleukin (IL)-1b, IL-6, IL-8, IL-10, and TNF-a; and granulocyte-macrophage colony-stimulating factor (Kostulas et al. 1998).
In this study, the patients with acute ischemic stroke showed a significant higher level of IL-8 in the first 48 h post stroke than controls. This was in agreement with previous studies (Kostulas et al. 1998; Domac and Misirli 2008). Moreover, Kostulas et al. (1998) stated that increased concentrations of IL-8 can be detected intrathecally in patients with ischemic stroke. However, it was not restricted to the CNS. This upregulation of IL-8 mRNA expression occurred early within the first few days after onset of symptoms and remained elevated up to 1 month.
It was postulated that IL-8 is a neutrophil chemotaxic and activating factor as it stimulates the binding of neutrophils to the receptors which causes a conformational change in the integrin molecules, and facilitates adhesion and transmigration (Adams and Lloyd 1997). It has been clearly shown that local expression of IL-8 in the ischemic brain establishes a concentration gradient over the blood-brain barrier, and as a result of movement of migrating cells toward this gradient, the neutrophils rapidly penetrate into the brain parenchyma and cause local inflammation (Yamasaki et al. 1995).
In this study, the patients with moderate disability assessed by NIHSS showed significantly higher serum IL-8 level than those with minor disability as well as there was a significant positive correlation between NIHSS and serum IL-8 level which was in agreement with other previous studies (Chernykh et al. 2016; Li et al. 2015). Chernykh et al. (2016) stated a significant positive correlation of stroke severity with production of IL-8 which was not influenced by the duration of post-stroke period. These findings could be explained by that the serum level of IL-8 is corresponding to the extent of cerebral ischemia, cortical damage, and the resulting disability (Li et al. 2015).
On the other side, there was no significant difference between patients with no, slight, and moderate disability assessed by mRS as regards IL-8 in this study. This was in contrast to others (Domac and Misirli 2008) who found higher serum of IL-8 in the patient with higher disability (mRS scores ≥ 3). This contradiction between NIHSS and mRS results could be explained by that 52% of the patients had no disability on mRS scale and 20% had moderate disability versus about 50% of the patients had moderate disability on NIHSS. Moreover, the NIHSS appeared more sensitive than mRS in evaluation disability in the acute stage of ischemic stroke (Roberts et al. 1998).
Several studies have also focused on biomarkers to predict stroke outcome and treatment response, which can be completely different between patients. Stroke prognosis might also influence medical decisions about sending stroke patients to specialized stroke units, palliative care, and rehabilitation programs or deciding the best moment for discharge (Simats et al. 2016).
Despite the fact that most of these inflammatory biomarkers are not specific to ischemic stroke, the levels of several inflammatory mediators correlate with stroke severity and outcome. Inflammatory biomarkers such as CRP or several pro-inflammatory cytokines, especially IL-6, have been widely associated with poor functional outcome after cerebral ischemic events (Counsell and Dennis 2001).
C-reactive protein (CRP) is a biomarker of inflammation and may reflect progression of vascular disease. Conflicting evidences suggested CRP may be a prognostic biomarker of ischemic stroke outcome. Most studies that have examined the relationship between CRP and ischemic stroke outcome have used mortality or subsequent vascular events as the primary outcome measure (VanGilder et al. 2014). A recently published prospective case-control study also reported that an elevated CRP level at admission was an independent predictor of functional outcome in the first month following acute ischemic stroke (Abubakar et al. 2013).
It was postulated that estimation of proinflammatory serum biomarkers such as high-sensitivity CRP (IL-6) in acute stroke would be highly beneficial in assessing the care pathway for patients and their treatment options, as the most important challenge facing physicians is to reduce the unacceptable burden of stroke (Bharosay et al. 2011). However, there was no significant difference in disability assessed by NIHSS or mRS between the patients with positive and negative CRP in this study. In agreement with this result, Idicula et al. (2009) had suggested no association between high CRP level at admission and poor outcome. The lack of association might be attributed to the short outcome period (in the first few days).
Another explanation for lack of correlation could be due to measurement of low-sensitivity CRP in the patients of this study in spite of high-sensitivity CRP (hs-CRP) assay, this could not be sufficiently sensitive to measure blood levels of CRP within the normal range (< 10 mg/L); however, the development of high-sensitivity assays for CRP (hs-CRP) had permitted detection of even mild elevation of CRP, even within the normal range (Roberts et al. 2000).
The limitation of this study included lack of measurement of body mass index (BMI) as an indicator of obesity, and its correlation with the serum level of IL-8 as a major risk factor of ischemic stroke should be done in further studies.
