Multiple Sclerosis (MS) is a chronic, autoimmune disease of the central nervous system. MS is believed to be a Th1 inflammatory disease, speculated to be mediated by CD4+ T lymphocytes. The specific contribution of monokines to disease has not been extensively studied in MS. I thus hypothesize that Th1 regulatory monokine levels are elevated in MS patients, and these increased levels correlate to disease severity. This project deals with the quantitation of regulatory monokine mRNA and protein levels in MS patients and their subsequent comparison to healthy control levels. The influence of cytokine-directed immunotherapy, specifically IFN-beta1a and IL-10, on these monokine levels is also addressed. Highly enriched monocytes were isolated and separately cultured for 24 hours in the presence of RPMI media alone, or supplemented with IFN-beta1a or IL-10. Protein and mRNA levels were determined for various monokines by intracellular staining, ELISA, and Riboquant RNase Protection Assay. Increased monokine levels of IL-1, IL-6, IL-12, and TNF-alpha were found to correlate significantly with increased MS disease severity as compared to healthy control levels. IL-10 and IFN-gamma were also detected in MS patient samples, however these levels did not differ significantly from healthy control levels. IL-10 24-hour exposure was found to significantly reduce all elevated MS patient monokine levels. IFN-beta1a showed minimal effects in reducing elevated MS patient monokine levels, and in certain patients boosted their Th1 and proinflammatory monokine levels. These findings suggest a role for monocytes and monokines in the immunopathogenesis of MS, and also indicate further study into IL-10 as a potential MS therapy may be warranted.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/9335 |
| Date | January 2000 |
| Creators | Graham, Angela L. |
| Contributors | Filion, L., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 80 p. |
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