Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using PubMed to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients.

     

Carcinogenesis and cyclooxygenase: the potential role of COX-2 inhibition in upper aerodigestive tract cancer

Cyclooxygenase-2 (COX-2) is upregulated in a number of epithelial cancers, including in upper aerodigestive tract (UADT) premalignant and malignant lesions. The purpose of this review is to provide a comprehensive examination of the potential of COX-2 inhibition in prevention of UADT premalignant and malignant disease. A Medline and Cancerlit literature search was conducted for the period 1993-2002, and identified literature was reviewed. There is evidence from in vitro studies, as well as animal models, that inhibition of COX-2 may suppress carcinogenesis by affecting a number of pathways of carcinogenesis, promoting apoptosis and inhibiting angiogenesis. Preliminary studies of gastro-intestinal (GI) carcinogenesis suggest that COX-2 inhibitors may represent an approach to the chemoprevention of epithelial cancers. COX-2 inhibitors may have a potential role in chemoprevention of UADT cancer, and clinical trials appear warranted.