AUTHOR=Khaibullin Timur , Ivanova Vilena , Martynova Ekaterina , Cherepnev Georgy , Khabirov Farit , Granatov Evgenii , Rizvanov Albert , Khaiboullina Svetlana 

TITLE=Elevated Levels of Proinflammatory Cytokines in Cerebrospinal Fluid of Multiple Sclerosis Patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00531

DOI=10.3389/fimmu.2017.00531

ISSN=1664-3224

ABSTRACT=Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by chronic brain inflammation. Leukocyte infiltration of brain tissue causes inflammation, demyelination and the subsequent formation of sclerotic plaques, which are a hallmark of MS. Activation of proinflammatory cytokines is essential for regulation of lymphocyte migration across the blood brain barrier. We demonstrate increased levels of many cytokines, including IL2Ra, CCL5, CCL11, MIF, CXCL1, CXCL10, IFNγ, SCF and TRAIL, were upregulated in CSF, whereas IL17, CCL2, CCL3, CCL4 and IL12(p40) were activated in MS serum. Interaction analysis of cytokines in CSF demonstrated a connection between IFNγ and CCL5 as well as MIF. Many cells can contribute to production of these cytokines including CD8 and Th1 lymphocytes and astrocytes. Therefore, we suggest that IFNγ released by Th1 lymphocytes can activate astrocytes, which then produce chemoattractants, including CCL5 and MIF. These chemokines promote an inflammatory milieu and interact with multiple chemokines including CCL27 and CXCL1.  Of special note, upregulation of CCL27 was found in CSF of MS cases. This observation is the first demonstrate CCL27 as a potential contributor of brain pathology in MS. Our data suggests that CCL27 may be involved in activation and migration of autoreactive encephalitogenic immune effectors in the brain. Further, our data supports the role of Th1 lymphocytes in the pathogenesis of brain inflammation in MS, with several cytokines playing a central role.