Interleukin 23 levels are increased in carotid atherosclerosis – A possible role for the IL-23/IL-17 axis?
Abbas A, Gregersen I, Holm S, Daissormont I, Bjerkeli V, Krohg-Sørensen K, et al. Interleukin 23 Levels Are Increased in Carotid Atherosclerosis: Possible Role for the Interleukin 23/Interleukin 17 Axis. Stroke. 2015
The world of immunology and elucidation of cytokine pathways is not usually the focus of the vascular neurologist, but perhaps our attention should be redirected. It is well established that atherosclerosis is a state of inflammation and prior studies have shown an increased expression of IL-23 in carotid lesions, with particularly high levels in symptomatic patients. Targeting of IL-23, a member of the IL-12 family of cytokines with pro-inflammatory properties, is already underway in other autoimmune diseases including psoriasis, inflammatory bowel disease and rheumatoid arthritis. How is this interleukin, with its role in producing IL-17 related to cerebrovascular disease?
Abbas et. al in their study reinvestigated the association of IL-23 to atherosclerosis and sought to better establish any relationship between expression and cerebrovascular disease. 177 patients with internal carotid stenosis (≥50%) were recruited and classified according to symptoms: 69 patients had a stroke/TIA/amaurosis fugax ipsilateral to the stenosed carotid artery in the prior 2 months and 108 patients either had symptoms >2 months or had no symptoms. The patients were compared to 24 healthy controls from the same area of Norway. Plasma samples were obtained by venipuncture. Plaque samples were obtained for examination from 68 of the patients with carotid atherosclerosis and compared to non-atherosclerotic control vessels of organ donors.
Those with carotid atherosclerosis (177) were found to have markedly raised plasma IL-23 levels compared to controls (24). Notably, the level of IL-23 increased in a step wise fashion with the highest plasma levels in those with the most recent symptoms (<1month). Even those without symptoms still had higher levels of IL-23 than healthy controls. When the plaque samples were evaluated, IL-23 as well as IL-23 receptors (R) were 18 fold higher in those with atherosclerosis. However, there was no association between levels of IL-23 and presence or absence of symptoms.
In order to better elucidate the role of IL-23, plasma dendritic cells, peripheral blood mononuclear cells and monocytes from patients with carotid atherosclerosis were evaluated. The investigators found those with carotid atherosclerosis had increased levels of IL-23/IL-23R in dendritic cells as well as increase release of IL-17 from mononuclear cells when stimulated with IL-23 in comparison to healthy controls. IL-23 promoted release of tumor necrosis factor (TNF) only in those with carotid atherosclerosis.
Recent data indicate that IL-23 is a dominant cytokine controlling inflammation in peripheral tissues and joints, but what role does it have to play in stoke? This study suggests that IL-23 plays a unique role in the patient with atherosclerosis compared to healthy controls. The study has limitations such as a small control sample size, but is it possible that the release of IL-23, the interaction with its receptor or the stimulation of IL-17 represent three potential targets for new therapies? Could we control some of the sequela of stroke by a modulation of this cascade? While other trials targeting the inflammatory response in stroke are underway using Methotrexate and Tysabri, perhaps further research should be directed at the IL-23/IL-17 cascade in hopes that in vivo trials could provide even more exciting results.