Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 575 587 Saeid Khosropour Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Elahe Shahvarooghi Departement of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran Hossein Rezaeizadeh Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran Maryam Esmaeelzadeh Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran 2023 03 06 2023 08 22 Multiple sclerosis (MS) is an inflammatory disorder impacting the central nervous system, with cytokines significantly influencing its pathogenesis. This study investigates the effect of curcumin and its semisynthetic derivative F-curcumin on cytokine gene expression in autoimmune encephalomyelitis (EAE) mouse models of MS. We assessed the expression levels of specific cytokines including interleukin (IL)-1β, IL-4, IL-10, IL-17, interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β), alongside key transcription factors for helper T cells (T-bet, GATA-3, RORγt, and FoxP3) in both the spinal cord and spleen. Treatment with curcumin and F-curcumin significantly ameliorated the severity and onset of EAE. Notably, mice administered with either compound showed a substantial decrease in the expression of genes encoding IL-1 (2 folds), IFN-γ (2 and 4 folds), and IL-17 (2.5 and 3.5 folds), alongside a marked increase in TGF-β (7 folds) and IL-10 (4 and 6 folds) levels. Additionally, the gene expression of T cell-derived transcription factors nearly mirrored the changes observed in pro-inflammatory and anti-inflammatory cytokines across the groups. The F-curcumin-treated group exhibited more pronounced results. In conclusion, curcumin and F-curcumin significantly modulate cytokine gene expression during EAE induction, potentially alleviating inflammation in MS, with F-curcumin showing a more substantial effect. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3787 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3787/2017