Treatment with relaxin reduces disease symptoms and enhances neuroprotection and remyelination in murine experimental autoimmune encephalomyelitis

摘要

The use of glucocorticoid agonists in treating acute attacks of multiple sclerosis is well established. Relaxin, a member of the insulin super family is a pleiotropic hormone capable of influencing multiple pathways which include the glucocorticoid receptor and relaxin family peptide receptors 1 and 2. In addition to the action of relaxin on the glucocorticoid receptor, activation of the relaxin receptors have additional anti-inflammatory and immuno-modulating effects. In the present study we investigated the effectiveness of relaxin in treating a murine model of MS, experimental allergic encephalomyelitis. Disease was induced and the mice were scored daily for clinical signs of disease (0=normal, 3=hind limb paralysis, 5=found dead). When a clinical score of 3 or higher was reached, relaxin was continuously infused for 8 days. Plasma for RT-PCR and spinal cords for histology were collected. The levels of CCR2, CCR5, CCR7, interleukins-6 and 17 were analyzed using quantitect primers and SYBR green based RT-PCR kits. Spinal cords were formalin fixed, paraffin embedded, sectioned and scored for myelin content, macrophage infiltration, neurofilaments, gliosis and markers of remyelination. The results of the study show that continuous infusion of relaxin significantly reduced the clinical signs of disease, decreased mRNA expression of pro-inflammatory cytokines and chemokine receptors. Histological staining and immune-histochemistry of the spinal cords showed that relaxin treatment lead to a decrease in lesion load and size and macrophage infiltration, preserved myelin and neurofilaments, reduced gliosis and promoted remyelination.