Elevated Systemic IL-6 Levels in Patients with Aneurysmal Subarachnoid Hemorrhage Is an Unspecific Marker for Post-SAH Complications

Abstract

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is still a fatal and morbid disease, although bleeding aneurysms can be secured in almost all cases. Occurrence of post-SAH complications including cerebral vasospasm, delayed cerebral ischemia, hydrocephalus, epilepsy, and infections are the main determinants of clinical outcome. Hence, it is important to search for early predictors for specific post-SAH complications to treat these complications properly. Both cellular and molecular (cytokines) inflammation play a key role after aSAH during the phase of occurrence of post-SAH complications. Interleukin-6 (IL-6) is a well-known cytokine that has been extensively analyzed in cerebrospinal fluid (CSF) of patients after aSAH, but detailed studies exploring the role of systemic IL-6 in aSAH associated complications and its impact on early clinical outcome prediction are lacking. The current study aims to analyze the systemic IL-6 levels over two weeks after bleeding and its role in post-SAH complications. Methods: We recruited 80 aSAH patients prospectively who underwent peripheral venous blood withdrawal in serum gel tubes. The blood was centrifuged to harvest the serum, which was immediately frozen at −80 °C until analysis. Serum IL-6 levels were quantified using Immulite immunoassay system. Patient records including age, gender, post-SAH complications, aneurysm treatment, and clinical outcome (modified Rankin scale and Glasgow outcome scale) were retrieved to allow different subgroup analysis. Results: Serum IL-6 levels were significantly raised after aSAH compared to healthy controls over the first two weeks after hemorrhage. Serum IL-6 levels were found to be significantly elevated in aSAH patients presenting with higher Hunt and Hess grades, increasing age, and both intraventricular and intracerebral hemorrhage. Interestingly, serum IL-6 was also significantly raised in aSAH patients who developed seizures, cerebral vasospasm (CVS), and chronic hydrocephalus. IL-6 levels were sensitive to the development of infections and showed an increase in patients who developed pneumoniae. Intriguingly, we found a delayed increase in serum IL-6 in patients developing cerebral infarction. Finally, IL-6 levels were significantly higher in patients presenting with poor clinical outcome in comparison to good clinical outcome at discharge from hospital. Conclusion: Serum IL-6 levels were elevated early after aSAH and remained high over the two weeks after initial bleeding. Serum IL-6 was elevated in different aSAH associated complications, acting as a non-specific marker for post-SAH complications and an important biomarker for clinical outcome at discharge.

Spontaneous Aneurysmal Subarachnoid Hemorrhage and Related Cortisol and Immunologic Alterations: Impact on Patients' Health-related Quality of Life

“…However, studies exist suggesting a controversial effect on outcome. [38][39][40][41] Finally, two thorough reviews of the literature highlighted the partly controversial existing data and suggested screening for hypopituitarism after SAH and TBI as well as a possible role for neuromodulation using cytokines. 14,42 Major Limitations of the Study Sufficient HRQoL data were acquired in only 50% of the overall eligible patients in the 2-year study period.…”

Elevated Systemic IL-10 Levels Indicate Immunodepression Leading to Nosocomial Infections after Aneurysmal Subarachnoid Hemorrhage (SAH) in Patients

“…Aneurysmal subarachnoid hemorrhage (SAH) is associated with a mortality rate of around 40-50% [1,2]. Despite successful aneurysm obliteration from the systemic circulation, a very high proportion of SAH patients confront life-threatening complications, and more than one-third of SAH patients develop systemic or local infections [3][4][5][6][7][8][9]. Post-SAH immunodepression may influence occurrence of infections.…”

Increased interleukin-6 levels in neuron-derived plasma small extracellular vesicles in patients with aneurysmal subarachnoid hemorrhage

“…Yet another study showed that IL-6 in CSF could be a useful diagnostic tool for predicting shunt dependency in aSAH patients with acute hydrocephalus [33]. Serum IL-6 levels were elevated, and were associated with prognosis in aSAH patients [26,34]. However, many previous studies also showed that determining the IL-6 levels in blood circulation may not be sufficient [30,35].…”