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

Abstract

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.

<p>Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis</p>

“…reduced the production of IFN-γ and IL-12 approximately by 25% and 60%, respectively. 43 In the present study, intravenous injection with NHNK (twice a week for 3 weeks) declined mean clinical score by 20% and reduced the production of IFN-γ and IL-12 by 50% and 20%, respectively. On the basis of these results, we speculate that the efficacy of intravenous NHNK therapy against EAE may be comparable to that of fingolimod and mitoxantrone.…”

Immunomodulatory effects of licochalcone A on experimental autoimmune encephalomyelitis

“…First, EAE was induced in C57Bl/6 mice and splenocytes were obtained after 20 days of MOG 35–55 immunization, because according to literature[18,19] the maximum immune response occurs around day 17 until 20 after induction of EAE. Then, the spontaneous or stimulated (ConA and MOG 35–55 ) production of both oxygen radicals (H 2 O 2 and NO) and cytokines (TNF‐α, IFN‐γ and IL‐17) was analysed after in‐vitro incubation with LicoA (at non‐cytotoxic concentrations).…”

“…It has been reported that IFN‐γ (Th1 cytokine), IL‐17 (Th17 cytokine) and TNF‐α play important roles in the induction and severity of MS and EAE [7,19,30]. During the acute phase of EAE, IFN‐γ and TNF‐α appear, and the level of expression parallels the severity of clinical signs and degree of inflammatory cells infiltration [31,32].…”

“…In addition, administration of IFN‐γ to MS patients exacerbates the disease. In addition, the deficiency of IL‐17 or the use of IL‐17 blocking antibodies prevented the development or reduced the severity of EAE [19,30]. Therefore, it can be assumed that LicoA reduced the severity of EAE through IFN‐γ, IL‐17 and TNF‐α inhibition.…”

“…Groups of five mice were subcutaneously immunized at the tail base with 100 μg of myelin oligodendrocyte glycoprotein peptide (MOG) 35–55 (Sigma Chemical Co., Saint Louis, MO, USA), emulsified with complete Freund's adjuvant (CFA) (v/v) (Sigma Chemical Co.) and supplemented with 400 μg of attenuated Mycobacterium tuberculosis H37RA (Difco, Detroit, MI, USA). Pertussis toxin 300 ng/animal (Sigma Chemical Co.) was injected intraperitoneally on the day of immunization and 48 h later [18,19]. Non‐immunized mice were used as control.…”