Intravenous immunoglobulin (IVIg) has been used to treat a variety of autoimmune disorders including multiple sclerosis (MS); however, its mechanism of action remains elusive. Our results demonstrate a novel finding wherein IVIg treatment induces a dramatic surge (>1000-fold increase) in the levels of IL-11 in the circulation and that the liver is the organ of increased IL-11 transcription. Furthermore, we show that IL-11Rα knockout mice, although initially protected, become resistant to protection by IVIg during experimental autoimmune encephalomyelitis (EAE) and develop disease with a similar incidence and severity as control-treated IL-11Rα-/- mice. The inability of IVIg to prevent EAE in IL-11Rα-/- mice correlated with a failure of this agent to decrease IL-17 production by myelin-reactive T-cells in the draining lymph nodes. Finally, we show that IL-11 can directly inhibit IL-17 production by lymph node cells in culture. Together, these results implicate IL-11 as an important immune effector of IVIg in the amelioration of EAE.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/42837 |
| Date | 22 November 2013 |
| Creators | Figueiredo, Carlyn |
| Contributors | Branch, Donald R. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0023 seconds