Neuroinflammation After Stroke: Considering the Role of IL-6 on a Broader Canvas

Zahra Sadat  Mousavi Bafrouei; Mahdieh  Rahmani; Nazanin  Nasiri; Seyed Mehrad  Razavi; Zahra  Najafi Arab; Zahra  Nikbakht; Nematollah  Jaafari; Farshad  Hashemian

doi:10.18502/jpc.v13i1.18405

Zahra Sadat Mousavi Bafrouei Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Mahdieh Rahmani Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
Nazanin Nasiri Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Seyed Mehrad Razavi Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Zahra Najafi Arab Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Zahra Nikbakht Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Nematollah Jaafari Université de Poitiers, Unité de recherche clinique intersectorielle Pierre Deniker du Centre Hospitalier Henri Laborit F-86022 France, Groupement De Recherche CNRS 3557, Poitiers, France.
Farshad Hashemian Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

DOI: https://doi.org/10.18502/jpc.v13i1.18405

Keywords: Interleukin-6; Ischemic Stroke; Hemorrhagic Stroke; Neuroinflammation

Abstract

Cerebrovascular diseases, including ischemic and hemorrhagic strokes, rank among the leading causes of worldwide mortality and long-term morbidity. An acute systemic inflammatory reaction is one of the primary acute-phase responses that occur following the onset of a stroke. Elevated expression of inflammatory markers such as cytokines can be observed early after a stroke's onset and may negatively influence the outcome. Interleukin-6 (IL-6) is considered a pleiotropic cytokine with both pro-inflammatory and anti-inflammatory effects and plays a crucial role in the inflammatory cascade following a stroke. IL-6 is essential for regulating the immune response. However, during the acute phase of a stroke, its overproduction can promote inflammation by acting as a proinflammatory cytokine, potentially exacerbating both the disease progression and the inflammatory response. Despite numerous investigations, the exact role and mechanism of action of IL-6 after a stroke remain complex and have yet to be fully explained. The present narrative review aims to assess serum and cerebrospinal fluid changes in IL-6 during different phases of the disease in both ischemic and hemorrhagic strokes and their possible correlation with short-term and long-term functional and neurological outcomes. We explore the potential application of IL-6 as a prognostic factor for diagnosis, recognition of subtypes, assessment of stroke severity, and prediction of outcomes. In this narrative review, peer-reviewed journal articles from 1990 to 2022 were searched on PubMed, MEDLINE, ScienceDirect, and Google Scholar to identify original studies. Several relevant articles were then selected based on their comprehensiveness and informativeness. Results suggest that IL-6 levels peak during the acute phase of both ischemic and hemorrhagic strokes, with elevated concentrations correlating with worse clinical outcomes, including poorer functional recovery and an increased risk of complications. The findings underscore the potential value of IL-6 as a biomarker for early prognostication and guiding clinical decision-making. In conclusion, IL-6 shows potential as a prognostic tool and therapeutic target in stroke management. However, its exact role remains unclear, and further research is needed to better understand its mechanisms and determine the optimal timing for measurement to ensure accurate predictions.