Aims: Inflammatory cytokines, particularly tumour necrosis factor-α (TNFα), are thought to promote arterial disease through a variety of mechanisms leading to arteriosclerosis and atherosclerosis. We reviewed the existing evidence of the effect of anti-TNFα treatment on arteriosclerosis and atherosclerosis in chronic inflammatory disease. Methods:We performed a systematic review of studies examining effects of monoclonal antibodies against TNFα on subclinical measures of arteriosclerosis (arterial pulse wave velocity) and atherosclerosis (endothelial function measured by flowmediated dilation or forearm blood flow responses to endothelium-dependent agonists, and common carotid intima-media thickness). Results:We identified 60 studies (of 854 potential studies identified using a systematic search) in which effects of anti-TNFα biologics on these measures were assessed in patients receiving anti-TNFα therapy for a clinical indication (usually an inflammatory disease such as an inflammatory arthritis, psoriasis or inflammatory bowel disease). Of these, only 6 were randomised clinical controlled trials. Whilst many observational studies and noncontrolled studies reported positive findings, positive finding were reported in only 1 of 6 randomised clinical controlled trials. Conclusions:There is no strong evidence for an effect of anti-TNFα biologics on the subclinical measures of arteriosclerosis or atherosclerosis examined in this review.This does not exclude a positive effect of TNFα biologics on clinical outcomes through alternate pathways including those induced by remission of the primary inflammatory disease.

Myelin, once thought of as a simple insulating sheath, is now known to be a complex, dynamic structure. It has multiple functions in addition to increasing conduction velocity, including reducing the energetic cost of action potentials, saving space, and metabolic functions. Myelin is also notable for likely having arisen independently at least three times over the course of evolutionary history. This article reviews the available evidence about the evolution of myelin and proposes a hypothesis of how it arose in vertebrates. It then discusses the evolutionary trade-offs associated with myelination and suggests a possible animal model for further study of this phenomenon. Finally, it briefly covers the neural regulation of myelination before discussing possible roles of myelin in human social cognition and evolution, and the relevance of this to human disease.