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Cytokine Profile in Patients with Progressive Multiple Sclerosis and Its Association with Disease Progression and Disability

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Abstract

Inflammation is the driving force for brain injury in patients with multiple sclerosis (MS). The objective of the present study is to delineate the serum cytokine profile in patients with progressive MS in a Southern Brazilian population compared with healthy controls and patients with relapsing-remitting MS (RRMS) and its associations with disease progression and disability. We included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-10, IL-4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay. IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in progressive MS than in controls. Increased IL-1β and IFN-γ and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients with progressive MS with disease progression presented higher TNF-α, IFN-γ, and IL-10 levels than those without disease progression. Patients with progressive MS with disease progression showed a higher frequency of positive gadolinium-enhanced lesions in MRI; higher TNF-α, IFN-γ, and IL-17 levels; and decreased IL-12 levels compared with RRMS patients with progression. There was a significant inverse correlation between IL-10 levels and EDSS score in patients with progressive MS. The results underscore the complex cytokine network imbalance exhibited by progressive MS patients and show the important involvement of TNF-α, IFN-γ, and IL-17 in the pathophysiology and progression of the disease. Moreover, serum IL-10 levels were inversely associated with disability in patients with progressive MS.

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Acknowledgments

The study was supported by grants from Coordination for the Improvement of Higher Level of Education Personnel (CAPES) of Brazilian Ministry of Education, Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq), and State University of Londrina (PROPPG). We thank the University Hospital of State University of Londrina and HUTec Foundation for technical and administrative supports.

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Authors and Affiliations

  1. Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil

    Ana Paula Kallaur, Sayonara Rangel Oliveira, Daniela Frizon Alfieri, Tamires Flauzino, Josiane Lopes & Wildea Lice de Carvalho Jennings Pereira

  2. Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, State University of Londrina, Av. Robert Koch, 60, CEP 86.038-440, Londrina, Paraná, Brazil

    Andréa Name Colado Simão & Edna Maria Vissoci Reiche

  3. Outpatient Clinic for Multiple Sclerosis, University Hospital, State University of Londrina, Londrina, Paraná, Brazil

    Wildea Lice de Carvalho Jennings Pereira, Caio de Meleck Proença & Damacio Ramón Kaimen-Maciel

  4. Department of Clinical Analysis, Laboratory of Immunogenetics, State University of Maringá, Maringá, Paraná, Brazil

    Sueli Donizete Borelli

  5. Department of Clinical Medicine, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil

    Damacio Ramón Kaimen-Maciel

  6. Impact Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia

    Michael Maes

  7. Department of Psychiatry, King Chulalongkorn Memorial Hospital, Chulalongkorn, Bangkok, Thailand

    Michael Maes

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  1. Ana Paula Kallaur
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Kallaur, A.P., Oliveira, S.R., Simão, A.N.C. et al. Cytokine Profile in Patients with Progressive Multiple Sclerosis and Its Association with Disease Progression and Disability. Mol Neurobiol 54, 2950–2960 (2017). https://doi.org/10.1007/s12035-016-9846-x

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