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Stimulated PBMC-produced IFN-γ and TNF-α are associated with altered relapse risk in multiple sclerosis: Results from a prospective cohort study


Simpson Jr, S and Stewart, N and van der Mei, I and Otahal, P and Charlesworth, J and Ponsonby, AL and Blizzard, L and Dwyer, T and Pittas, F and Gies, P and Taylor, B, Stimulated PBMC-produced IFN-γ and TNF-α are associated with altered relapse risk in multiple sclerosis: Results from a prospective cohort study, Journal of Neurology, Neurosurgery and Psychiatry, 86 pp. 200-207. ISSN 0022-3050 (2015) [Refereed Article]

Copyright Statement

Copyright 2014 BMJ Publishing Group

DOI: doi:10.1136/jnnp-2013-307336


Background: Altered reactivity of peripheral blood mononuclear cells (PBMC) and their production of cytokines may affect multiple sclerosis (MS) clinical course. We assessed the relationship of stimulated PBMC-produced IFN-γ, TNF-α, IL-4 and IL-10 in modulating relapse risk using a prospective cohort with established relapsing-remitting MS.

Methods: Cytokine production from PBMCs taken in summer and winter was measured by ELISA. Predictors of cytokines assessed by multilevel mixed-effects linear regression. Predictors of relapse assessed by survival analysis.

Results: Increasing IFN-γ was associated with increasing relapse risk, while increasing TNF-α reduced relapse risk after adjusting for IFN-γ. IL-10 and IL4 were not consistently associated with relapse risk. IFN-γ's effects on relapse were greatly attenuated by immunomodulatory therapies, by summer season and by higher serum vitamin D, whereas TNF-α's inverse association with relapse was only present in these circumstances. The TNF-α inverse association with relapse was only present among persons carrying the wild-type of the functional SNP rs1800693 in TNFRSF1A that has been previously associated with MS risk.

Conclusions: We found strong effects of IFN-γ and TNF-α on relapse risk, these differing by immunomodulatory therapy, season, and serum vitamin D, as well as by genotype. These results indicate altered reactivity of immune cells modulate MS disease.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Simpson Jr, S (Dr Steve Simpson JR)
UTAS Author:Stewart, N (Dr Niall Stewart)
UTAS Author:van der Mei, I (Professor Ingrid van der Mei)
UTAS Author:Otahal, P (Mr Petr Otahal)
UTAS Author:Charlesworth, J (Dr Jac Charlesworth)
UTAS Author:Blizzard, L (Professor Leigh Blizzard)
UTAS Author:Pittas, F (Dr Fotini Pittas)
UTAS Author:Taylor, B (Professor Bruce Taylor)
ID Code:91587
Year Published:2015 (online first 2014)
Web of Science® Times Cited:19
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-22
Last Modified:2017-11-06

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