ABSTRACT
A growing body of evidence suggests the anti-inflammatory and antitumor effects of parthenolide (PAR). Here we show that PAR treatment inhibits the initiation of experimental autoimmune neuritis (EAN), suppresses the production of TNF-α, IFN-γ, IL-1ß and IL-17, and decreases Th1 and Th17 cells at early time point. However, such anti-inflammatory effect vanishes later and PAR impedes the recovery of EAN in late phase, which is accompanied with inhibited apoptosis of inflammatory cells. Our results indicate that PAR plays dual roles in EAN and it is not proper to be applied in autoimmune diseases of nervous system.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Neuritis, Autoimmune, Experimental/drug therapy , Sesquiterpenes/therapeutic use , Analysis of Variance , Animals , Annexin A5/metabolism , Apoptosis/physiology , CD4-Positive T-Lymphocytes/pathology , Cell Proliferation/drug effects , Cell Proliferation/physiology , Cytokines/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Flow Cytometry , Forkhead Box Protein O3/metabolism , Freund's Adjuvant/toxicity , Lymph Nodes/pathology , Mycobacterium tuberculosis , Neuritis, Autoimmune, Experimental/etiology , Rats , Rats, Inbred Lew , Sciatic Nerve/pathologyABSTRACT
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.
Subject(s)
Curcumin/administration & dosage , Myasthenia Gravis, Autoimmune, Experimental/immunology , Myasthenia Gravis, Autoimmune, Experimental/psychology , Animals , B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Cytokines/metabolism , Female , Genes, MHC Class II , Inflammation Mediators/metabolism , Killer Cells, Natural/drug effects , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lymphocytes/drug effects , Lymphocytes/metabolism , Myasthenia Gravis, Autoimmune, Experimental/metabolism , Myasthenia Gravis, Autoimmune, Experimental/prevention & control , Natural Killer T-Cells/drug effects , Natural Killer T-Cells/metabolism , Rats , Rats, Inbred LewABSTRACT
OBJECTIVE: To To investigate the effect of acupuncture on the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), nitric oxide synthase (NOS) content and muscular tension of spasticity cerebral palsy rat model. METHODS: The rats with spastic cerebral palsy were randomly divided into the control group, model group and acupuncture group. After successful modeling, the muscular tension and the content of TNF-α, IL-6, CRP, NOS were measured. RESULTS: The serum TNF-α, IL-6, CRP, NOS content were significantly decreased in the acupuncture group (P<0.05). The low and high shear viscosity of whole blood of the acupuncture group were significantly lower than the control group and the model group (P<0.05). The erythrocyte electrophoresis indexes in the acupuncture group were significantly lower than that in the model group and the control group (P<0.05). Acupuncture significantly reduced the muscular tension of spastic cerebral palsy rat and increased the active extent in the paralytic extremity (P<0.05), but it could not be restored to normal level. Compared with the control group, the difference had significant (P<0.05). CONCLUSIONS: Acupuncture treatment can inhibit the release of inflammatory cells after brain injury, then reduce immune injury, relieve muscle spasms and reduce muscular tension.
Subject(s)
Acupuncture Therapy , Cerebral Palsy/blood , Cerebral Palsy/therapy , Cytokines/blood , Animals , Disease Models, Animal , Hemorheology/physiology , Male , Muscle Tonus/physiology , Rats , Rats, WistarABSTRACT
Statins have anti-inflammatory and immune-regulating properties. To investigate the effects of atorvastatin on experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome (GBS), atorvastatin was administered to Lewis rats immunized with bovine peripheral myelin in complete Freund's adjuvant. We found that atorvastatin ameliorated the clinical symptoms of EAN, decreased the numbers of inflammatory cells as well as IFN-γ(+) and IL-17(+) cells in sciatic nerves, decreased the CD80 expression and increased the number of CD25(+)Foxp3(+) cells in mononuclear cells (MNC), and decreased the levels of IFN-γ in MNC culture supernatants. These data provide strong evidence that atorvastatin can act as an inhibitor in EAN by inhibiting the immune response of Th1 and Th17, decreasing the expression of co-stimulatory molecule, and up-regulating the number of T regulatory cells. These data demonstrated that statins could be used as a therapeutic strategy in human GBS in future.
Subject(s)
Cytokines/metabolism , Heptanoic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Neuritis, Autoimmune, Experimental/drug therapy , Neuritis, Autoimmune, Experimental/immunology , Pyrroles/pharmacology , T-Lymphocyte Subsets/drug effects , Animals , Atorvastatin , Cattle , Female , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/immunology , Humans , Immunization , Interferon-gamma/metabolism , Interleukin-17/metabolism , Myelin Sheath/immunology , Neuritis, Autoimmune, Experimental/pathology , Rats , Rats, Inbred Lew , Sciatic Nerve/drug effects , Sciatic Nerve/pathology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Th1 Cells/drug effects , Th1 Cells/immunology , Th17 Cells/drug effects , Th17 Cells/immunologyABSTRACT
Dehydroepiandrosterone (DHEA) is an abundant adrenal steroid in serum of humans, and has been reported to have anti-inflammatory, anti-proliferative, and certain immune-regulating properties. Experimental autoimmune neuritis (EAN) is a Th1 cell-mediated animal model of Guillain-Barré syndrome (GBS) in humans. In the present study, DHEA was administered subcutaneously to Lewis rats immunized with bovine peripheral myelin (BPM) in Freund's complete adjuvant. Rats treated with DHEA displayed significant delay in onset, decreased inflammatory cell infiltration in the PNS. Benefit was associated with significant decreases in numbers of IFN-gamma and TNF-alpha expressing cells in the PNS, BPM-stimulated T cell proliferation and IFN-gamma, TNF-alpha-secretion in the spleen cells. Only 2 mg DHEA-treated EAN rats decreased peak clinical score. No significant difference of supernatant IL-10 was found among the treatment and control groups. These results suggest that DHEA can ameliorate the severity of EAN by suppressing the proliferation of autoreactive T cell and expression of pro-inflammatory cytokines.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Dehydroepiandrosterone/administration & dosage , Neuritis, Autoimmune, Experimental/drug therapy , Analysis of Variance , Animals , Cattle , Cell Proliferation/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay/methods , Female , Freund's Adjuvant , Interferon-alpha/metabolism , Interferon-gamma/metabolism , Myelin Sheath/immunology , Neuritis, Autoimmune, Experimental/etiology , Neuritis, Autoimmune, Experimental/immunology , Neuritis, Autoimmune, Experimental/pathology , Peripheral Nervous System Neoplasms/metabolism , Rats , Rats, Inbred Lew , T-Lymphocytes/drug effects , T-Lymphocytes/immunologyABSTRACT
AIM: To explore the effect of dehydroepiandrosterone (DHEA) on cellular immune response in experimental autoimmune neuritis (EAN). METHODS: 21 female Lewis rats were randomly divided into DHEA 0.5 mg treatment groups, 2 mg treatment groups and control group ( n=7). Treatment groups were subcutaneously injected every day with DHEA and the control group with the same level of DHEA dissolvent from day 5 post immunization (p.i) with bovine peripheral myelin (BPM) in Freund's complete adjuvant (CFA). The effects were assessed in terms of of the number of IFN-gamma, TNF-alpha positive cells in sciatic nerve sections, T-cell proliferation and inflammatory cytokines (IFN-gamma, TNF-alpha and IL-10) synthesis by draining lymph node and spleen cells at the height of clinical EAN. RESULTS: Rats treated with DHEA at different doses displayed significant decreases in numbers of IFN-gamma, TNF-alpha expressing cells in the PNS (P<0.05), BPM-stimulated T cell proliferation (P<0.05), IFN-gamma, TNF-alpha secretion in draining lymph node and spleen (P<0.05) compared to control group. No significant difference of supernatant IL-10 was found among the different groups (P<0.05). CONCLUSION: Administration with exogenous DHEA inhabits cellular immune response by suppressing the proliferation of autoreactive T-cell and production of pro-inflammatory cytokines in Lewis rats with EAN.
Subject(s)
Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Dehydroepiandrosterone/pharmacology , Dehydroepiandrosterone/therapeutic use , Immunity, Cellular/drug effects , Neuritis, Autoimmune, Experimental/drug therapy , Neuritis, Autoimmune, Experimental/immunology , Animals , Female , Interferon-gamma/metabolism , Interleukin-10/metabolism , Lymph Nodes/drug effects , Lymph Nodes/immunology , Random Allocation , Rats , Rats, Inbred Lew , Spleen/drug effects , Spleen/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
To detect a possible effect of dehydroepiandrosterone (DHEA) in the pathogenesis of experimental autoimmune myasthenia gravis (EAMG), DHEA (0.5 mg/rat) was administrated intraperitoneally to Lewis rats every other day from day 4 postimmunization (p.i.) to day 35 p.i. with Torpedo acetylcholine receptor (AChR) and Freund's complete adjuvant. Rats treated with DHEA had a lower clinical score (mean clinic score, 2 versus 0.5 on day 37 p.i.) and a lower body weight loss (mean body weight, 169 versus 142 g on day 37 p.i.) compared with control EAMG rats. DHEA treatment decreased serum anti-AChR IgG and IgG2b antibody titers on days 7, 14, and 21 p.i. and inhibited the levels of anti-AChR IgG antibody secreting cells (60%), accompanied by decreased IL-4 (33%) and augmented TGF-beta1-positive cells (41%) among lymph node mononuclear cells. These results obtained from EAMG in Lewis rats further encourage us to study DHEA treatment in human MG.