title: Systematic Review and Meta-Analysis of the Efficacy of Interleukin-1 Receptor Antagonist in Animal Models of Stroke: an Update.
abstract: Interleukin-1 receptor antagonist (IL-1 RA) is an anti-inflammatory protein used clinically to treat rheumatoid arthritis and is considered a promising candidate therapy for stroke. Here, we sought to update the existing systematic review and meta-analysis of IL-1 RA in models of ischaemic stroke, published in 2009, to assess efficacy, the range of circumstances in which efficacy has been tested and whether the data appear to be confounded due to reported study quality and publication bias. We included 25 sources of data, 11 of which were additional to the original review. Overall, IL-1 RA reduced infarct volume by 36.2 % (95 % confidence interval 31.6-40.7, n = 76 comparisons from 1283 animals). Assessments for publication bias suggest 30 theoretically missing studies which reduce efficacy to 21.9 % (17.3-26.4). Efficacy was higher where IL-1 RA was administered directly into the ventricles rather than peripherally, and studies not reporting allocation concealment during the induction of ischaemia reported larger treatment effects. The preclinical data supporting IL-1 RA as a candidate therapy for ischaemic stroke have improved. The reporting of measures to reduce the risk of bias has improved substantially in this update, and studies now include the use of animals with relevant co-morbidities.
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: McCann
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Fala
authors.initials: F
authors.lastname: Cramond
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Macleod
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. emily.sena@ed.ac.uk.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Sena
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1
keywords: Experimental validity; Focal cerebral ischaemia; Interleukin-1 receptor antagonist; Meta-analysis; Neuroprotection; Systematic review