RESUMEN
Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co-stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-γ and TNF-α) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells). Moreover, the administration of curcumin promoted the differentiation of B cells into a subset of B10 cells, increased the anti-R97-166 peptide IgG1 levels and decreased the relative affinity indexes of anti-R97-116 peptide IgG. In summary, curcumin effectively ameliorate EAMG, indicating that curcumin may be a potential candidate therapeutic agent for MG.
Asunto(s)
Curcumina/administración & dosificación , Miastenia Gravis Autoinmune Experimental/inmunología , Miastenia Gravis Autoinmune Experimental/psicología , Animales , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Femenino , Genes MHC Clase II , Mediadores de Inflamación/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Miastenia Gravis Autoinmune Experimental/metabolismo , Miastenia Gravis Autoinmune Experimental/prevención & control , Células T Asesinas Naturales/efectos de los fármacos , Células T Asesinas Naturales/metabolismo , Ratas , Ratas Endogámicas LewRESUMEN
Prophylactic oral administration of a novel immunomodulator (immunosuppressant), FTY720 (1 mg/kg, three times a week), completely prevented the development of experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 mice. EAMG has been used as an animal model for human myasthenia gravis, and was established by immunizing the mice with acetylcholine receptor (AChR) from Torpedo californica. FTY720 also suppressed the production of both anti-Torpedo californica AChR antibody and anti-mouse AChR autoantibody by the mice, which were observed in mice in which EAMG had become established. These results strongly suggest that FTY720 is a promising candidate for treatment of human myasthenia gravis.