Aim of the Study: Interferon-beta (IFNβ), multiple sclerosis (MS) drug for years, does not have therapeutic effects on each patient. Yet, a considerable portion has experienced no therapeutic response to IFNβ. Therefore, it is necessary to determine disease-specific biomarkers that affect drug response. Here, we aimed to determine the effects of interleukin 10 (IL10) and 23 (IL23A), as well as forkhead box P3 (FOXP3) genes on MS after IFNβ therapy.Materials and Methods: Peripheral blood mononuclear cells (PBMCs) of 42 MS patients were isolated to obtain CD4+ and CD25+ T cells. Both cell types were characterised by flow cytometry. To determine optimum drug concentration of IFNβ, cytotoxicity assays were assessed on each cell type for 4, 16, 24 and 48 hours respectively. Then, cells were cultured in the presence of 500 IU/mL of IFNβ. cDNA synthesis was performed after mRNA extraction. RT-PCR was performed to measure gene expressions of IL10, IL23A and FOXP3. Results were evaluated statistically.Results: It was found that the cytotoxic effect of IFNβ was more efficient as the exposure time was expanded regardless of drug concentration. Moreover, CD25+ T lymphocytes were more resistant to IFNβ. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48 hours in CD4+ T cells. For CD25+ T cells, the graded increase in FOXP3 was obtained while IL10 expression was gradually decreased throughout the drug intake.
Conclusion:Although a considerable change in expression was obtained, the longterm IFNβ effect on both genes and cells should be determined by follow-up at least a year.
What's knownIFNβ reduces the number of episodes and slows down the progression of disability in MS patients. However, the expected therapeutic response has not been experienced in the majority How to cite this article:
Aim of the Study: Multiple sclerosis (MS) is an autoimmune disorder
causing demyelination in axons. Available therapies target different
molecules, but not all have therapeutic effects on disease progression,
and this effect can only be seen after a long-time administration.
Interferon beta (IFN-β), an MS therapy for many years, slows down the
disease progression and reduces disease symptoms by targeting T cells.
Yet, a considerable portion of the patient has experienced no
therapeutic response to IFN-β. It is necessary to determine
disease-specific biomarkers which allow early diagnosis or treatment of
MS. Here, it was aimed to determine the effects of interleukin 10 (IL10)
and 23 (IL23A) as well as forkhead box P3 (FOXP3) genes on MS after
IFN-β therapy. Materials & Methods: Peripheral blood mononuclear cells
(PBMCs) were extracted to isolate CD4+ and CD25+ T cells. Cytotoxicity
assays were performed on each cell type for determining optimum drug
concentration. Then, cells were cultured and determined drug
concentration was administered to the cells to measure gene expressions
with RT-PCR. Results: It was found that the cytotoxic effect of IFN-β
was more efficient as the exposure time was expanded regardless of drug
concentration. Moreover, CD25+ T lymphocytes were more resistant to
IFN-β. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48h
in CD4+ T cells. For CD25+ T cells, the graded increase of FOXP3 was
obtained while IL10 expression was gradually decreased throughout the
drug intake, significantly. Conclusion: Although considerable change in
expression was obtained, the long-term IFN-β effect on both genes and
cells should be determined by follow-up at least a year. Keywords: MS,
IFN-β, IL23A, FOXP3, IL10, T cells
Multiple sclerosis (MS) is an autoimmune disorder causing demyelination in axons. Available therapies target different molecules, but not all have therapeutic effects on disease progression, and this effect can only be seen after a long-time administration. By the time, the disease progresses, and its outcomes become unbearable for the patient. IFN-β has been used in MS therapy for many years. It slows down the disease progression, also reduces disease symptoms by targeting T cells. Yet, a considerable portion of the patient has experienced no therapeutic response to IFN-β. Therefore, it is necessary to determine disease-specific biomarkers which allow early diagnosis or treatment of MS. Here, it was aimed to determine the effects of IL10, IL23A and
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