The Relationship between Protein C, Protein S and Cytokines in Acute Ischemic Stroke

Abstract

Objective: The role of inflammation in the pathogenesis of acute ischemic stroke is well known, but its association with the clinical picture is as yet unclear. Material and Methods: In our study, we measured the serum levels of the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) within the first 50 h of stroke in 60 acute stroke patients, and examined the association with the natural anticoagulants protein C and free protein S. We compared the results with a control group that consisted of 30 volunteers. We also correlated their levels with the clinical outcomes by using the Canadian Neurological Scale (CNS). Results: Neither stroke patients nor the control group had any elevations in IL-1β serum levels. However, the levels of serum IL-6 were significantly higher in stroke patients (13.7 ± 19.46 vs. 4.3 ± 15.88, p = 0.002). In addition, the protein S levels of patients were lower than those of the controls (84.36 ± 27.97 vs. 95.9 ± 25.64, p = 0.007). Although IL-6 showed negative correlation with protein S (r = –0.504, p = 0.000), the other studied cytokines TNFα and IL-1β did not correlate with these natural anticoagulants. Another negative correlation was found between IL-6 and CNS scores (r = –0.451, p = 0.000). In addition, both protein C and protein S positively correlated with CNS (r = 0.263, p = 0.042; r = 0.381, p = 0.003). There was also a positive correlation between protein C and protein S (r = 0.408, p = 0.001). Conclusions: Our results suggest that TNFα and IL1β serum levels are not elevated in the acute phase of stroke and have no correlation with the natural anticoagulants protein C and protein S. However, a decrease in free protein S may be related to elevated IL-6 levels. In addition, increased levels of IL-6 and reduced levels of protein C and protein S may play a role in acute ischemic stroke severity.

The Relationship between Insulin Resistance and Hypercoagulability in Acute Ischemic Stroke

“…Despite the fact that in one study, lower PC serum levels were found to have a definite correlation with stroke severity in a group of 43 patients [14], the same correlation could not be found in our previous study [25]. In the present study, there was no correlation between stroke severity and PC.…”

“…In those studies, natural anticoagulants were studied simultaneously, but their association with insulin resistance and stroke severity has not yet been examined. We have previously shown a positive correlation between PS levels and stroke severity [25]. In another study, AT III level on admission showed significant correlation with stroke severity and disability at 3 months but not in the acute phase [26].…”

“…PS and AT III levels were found to be lower in our patients with severe stroke while fibrinogen levels were increased. AT III [19,20,21,22,23] and PS [14,24,25] levels have previously been studied in patients with stroke, but with conflicting results. In those studies, natural anticoagulants were studied simultaneously, but their association with insulin resistance and stroke severity has not yet been examined.…”

“…These are patients with higher C-reactive protein and interleukin-6 levels, indicating inflammation [14,25,32,33,34]. Progression of stroke symptoms occurred in 76% of patients with decreased levels of the natural anticoagulants AT III, PC and PS, while this proportion was only 9% in those with normal levels.…”

Glucocorticoids Induce Protein S-Dependent Phagocytosis of Apoptotic Neutrophils by Human Macrophages

“…Production of both protein S and C4BP in the liver appears to be controlled by inflammatory mediators, including IL-6 (42,43). Levels of protein S are reduced in patients with ischemic stroke (44) and in patients with sepsis (45), possibly via the effects of TNF on endothelial cells (46). In contrast, glucocorticoids have been reported to elevate levels of protein S (47).…”