Anthraquinone derivative O,O′-bis-(3′-iodopropyl)-1,4-dihidroxyanthraquinone modulates immune response and improves experimental autoimmune encephalomyelitis

• Published in: International immunopharmacology Vol. 14; no. 2; pp. 127 - 132
• Main Authors: Alves, Caio C.S., Castro, Sandra B.R., Costa, Cristiane F., Dias, Alyria T., Alves, Chrystian J., Rodrigues, Michele F., Teixeira, Henrique C., Almeida, Mauro V., Ferreira, Ana Paula
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.10.2012; Elsevier
• Subjects: anthraquinone; Autoimmune diseases; Biological and medical sciences; Brain; CCL20 protein; Central nervous system; Chemokines; Cytokines; Cytotoxicity; Demyelination; EAE; Experimental allergic encephalomyelitis; Immune response; Inflammation; Inflammatory diseases; Interleukin 12; Interleukin 17; Interleukin 6; Medical sciences; mitoxantrone; Mitoxantrone analog; Multiple sclerosis; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myelin; Neurology; Pharmacology. Drug treatments; Spinal cord; EAE; Multiple sclerosis; Cytokines; Mitoxantrone analog; Chemokines; Antineoplastic agent; Autoimmunity; Animal model; Nervous system diseases; Anthraquinone derivatives; Immune response; Cytokine; Experimental allergic encephalomyelitis; Inflammatory disease; Chemokine; Alkylating agent; Antimetabolic; Analog; Central nervous system disease; Mitoxantrone
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2012.06.013

The present study investigated the effects of the anthraquinone derivative (O,O′-bis-(3′-iodopropyl)-1,4-dihidroxyanthraquinone — DIPDHAQ), mitoxantrone analog, in an experimental autoimmune encephalomyelitis (EAE) model. The results showed that DIPDHAQ treatment improved the clinical signs of the disease (n=10; vehicle: 3.8±0.3; DIPDHAQ: 1.4±0.9). The improvement was associated with a decrease of inflammatory cells, demyelination, IL-17, IFN-γ, IL-12p40, IL-6, TGF-β, CCL5 and CCL20 levels in the spinal cord. DIPDHAQ presented a low cytotoxicity when in vitro assays were performed. Therefore, the findings suggest a major role for DIPDHAQ in multiple sclerosis, disease characterized as an autoimmune inflammatory disorder against myelin proteins of the brain and spinal cord. The attenuation of inflammation and consequently improvement of clinical signs, involving a decrease of pro-inflammatory cytokines and the low cytotoxicity of DIPDHAQ, suggest that this compound could be used as an alternative treatment for autoimmune diseases in the central nervous system. [Display omitted] ►EAE is a murine autoimmune disease used to study multiple sclerosis. ►The use of a mitoxantrone analog (DIPDHAQ) in the treatment of EAE was investigated. ►DIPDHAQ treatment caused reduction of the EAE clinical signs. ►DIPDHAQ reduces infiltrated cells and demyelination in the spinal cords. ►DIPDHAQ reduces CCL5, CCL20, IL-6, IL-17, IL-12 and IFN-γ in the spinal cords.