Immunomodulatory effects of the filarial nematode product, ES-62, and phosphorylcholine-based small molecule analogues S3 and S5 in experimental autoimmune encephalomyelitis

  • Hazel June Ramage

Student thesis: Master's Thesis

Abstract

Background: Multiple sclerosis (MS) is an autoimmune inflammatory disease of which the pathophysiology includes pro-inflammatory responses of CD4+ T cells and macrophages and their associated cytokine cells with episodes of demyelination. The filarial nematode excretory secretory product ES-62 has shown anti-inflammatory activity in related autoimmune diseases and, along with small molecule derivatives (SMAs), could have therapeutic potential in MS. Methods: 7 to 9 week old C57BL/6 wild type mice were immunized to induce experimental autoimmune encephalomyeltis (EAE) with MOG35-55 and were treated with PBS (Control group), ES-62, or SMAs S5 or S3. Weight and EAE severity were monitored over 26 days, spleen and lymph node cells were cultured for cytokine analysis and spine and brain tissues stained for immunohistochemical analysis. A secondary in vivo experiment with an amended protocol was conducted to see if results were constant. Results: Treatment with ES-62, S5 or S3 showed a trend of reducing EAE severity in reducing recovery time and clinical scores but the results were not statistically significant. Our results show that S5 delayed disease onset, and S3 reducedanimal weight loss. However treatments with ES-62, S5 and S3 only showed a trend of reducing EAE severity in reducing recovery time and clinical scores but were not statistically significant when compared with control group. This is confirmed by the data of immunohistochemical staining of immune cells in the CNS. Cytokine assay suggests that there was a reduction of spleen and lymph node production of IL-17 and IFN╬│ by the S5 treated mice, and a reduction of IL-17 production in spleen cells by S3 treated mice (but again the difference was not statistically significant). Conclusion: The results of this thesis suggest that ES-62 and SMAs may play a protective role in EAE (and subsequently MS) with S5 potentially having the greater therapeutic effect. However, the experiments will need to be repeated to confirm any beneficial effects..
Date of Award10 Feb 2016
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorHui-Rong Jiang (Supervisor) & William Harnett (Supervisor)

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