Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission

Abstract

BackgroundA prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD) is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3) and CCL13 [monocyte chemoattractant protein (MCP)-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26) and MCPs (CCL13, CCL2, CCL8, and CCL7) in patients with NMOSD during remission.MethodsHealthy controls (HC; n = 30) and patients with MS (n = 47) and NMOSD (n = 58) in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β levels were detected using the human cytokine multiplex assay.ResultsPlasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1β, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD.ConclusionThe study indicates that in NMOSD, the overproduction of cytokines such as IL-1β and TNF-α during remission stimulates eosinophilic chemoattractants such as CCL13, CCL11, and CCL26, which in turn bind to their receptor (CCR3); this could lead to eosinophil hypersensitivity. These findings suggest that the elevated secretion of CCL13, CCL11, and CCL26 may be a critical step in eosinophil recruitment during NMOSD remission.

CCL26 regulates the proportion of CD4+CD25+FOXP3+�Tregs and the production of inflammatory factors in peripheral blood mononuclear cells following acute ischemic stroke via the STAT5 pathway

“…It is also known as macrophage inflammatory protein 4α, and it primarily plays a role in the regulation of eosinophils and T cells (9,10). Studies have confirmed that CCL26 can block the CCL2 response and CCL26 regulates the proportion of CD4 + CD25 + FOXP3 + Tregs and the production of inflammatory factors in peripheral blood mononuclear cells following acute ischemic stroke via the STAT5 pathway that specific molecules, such as pro-inflammatory cytokines, including interleukin (IL)-4, tumor necrosis factor (TNF)-α, IL-1β and interferon-γ can promote the synthesis of CCL26 in human monocytes (11)(12)(13). Thus, CCL26 is of utmost importance to the regulation of inflammatory responses.…”

CCL-11 or Eotaxin-1: An Immune Marker for Ageing and Accelerated Ageing in Neuro-Psychiatric Disorders

“…Huber et al (2018) reported that during the relapse phase, CCL-11 may be downregulated, while during the secondary progressive phase, CCL-11 is upregulated to achieve plateau levels [ 40 ]. In other studies, it was detected that CCL-11 (and CCL-5) may discriminate clinical subtypes of multiple sclerosis [ 76 , 77 , 78 ]. Thus, both CCL-11 and CCL-5 were lowered during the inflammatory phase as compared with progressive multiple sclerosis [ 77 ].…”

“…In other studies, it was detected that CCL-11 (and CCL-5) may discriminate clinical subtypes of multiple sclerosis [ 76 , 77 , 78 ]. Thus, both CCL-11 and CCL-5 were lowered during the inflammatory phase as compared with progressive multiple sclerosis [ 77 ]. Michael et al (2013) identified important chemokine profile markers including CCL-11 in patients with Neuromyelitis Optica (NMO), which were additionally different from those with MS [ 76 ].…”

“…These authors examined 29 aquaporin antibody-positive NMO patients and found CCL-11 (and CCL-4, G-CSF and myeloperoxidase) to be an important marker in NMO [76]. In NMO Spectrum Disorders (NMOSD), increasing production of TNF-α and interleukin-1β can stimulate CCL-11 binding to CCR3, which may lead to eosinophil hypersensitivity during remission, but not in MS [77]. Moreover, increased CCL-11 levels may be a critical step in NMOSD eosinophil restoration during remission while both elevated levels of CCL-11 and CCL-13 may be important in eosinophil recruitment during NMOSD remission [77,78].…”

Сoncentration of Anti-Inflamatory Cytokines in Cell Culture Supernatants in Children With Juvenile Idiopathic Arthritis

“…Цитокины -семейство полипептидных молекул, которые синтезируются клетками различных тканей организма, наиболее активными продуцентами этих молекул являются иммунокомпетентные клетки. ЦК регулируют ряд нормальных физиологических функций, защитные реакции при внедрении различных патогенов, а также развитие большинства патологических процессов, включая канцерогенез, сердечно-сосудистые нарушения, аутоиммунную патологию, аллергические реакции и другие [4,31,40,49]. В отношении регуляции воспалительного процесса ЦК разделяют на провоспалительные (инициирующие и усиливающие воспалительную реакцию) и противовоспалительные (подавляющие воспаление).…”