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Updated: Apr 30, 2026
A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data
Published on: December 9, 2015
Stimulated PBMC-produced IFN-γ and TNF-α are associated with altered relapse risk in multiple sclerosis: results from
Steve Simpson1, Niall Stewart2, Ingrid van der Mei1
1Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.
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.
Insights
Cytokine production from immune cells impacts multiple sclerosis (MS) relapse risk. Interferon-gamma (IFN-γ) increases risk, while Tumor Necrosis Factor-alpha (TNF-α) decreases it, influenced by treatment, season, vitamin D, and genetics.
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- Peripheral blood mononuclear cell (PBMC) reactivity and cytokine production influence multiple sclerosis (MS) progression.
- Understanding these immune cell dynamics is crucial for managing MS clinical course.
Purpose of the Study:
- To investigate the relationship between stimulated PBMC-produced cytokines (IFN-γ, TNF-α, IL-4, IL-10) and relapse risk in patients with established relapsing-remitting MS.
- To explore factors modulating these cytokine-relapse associations.
Main Methods:
- PBMC cytokine production (IFN-γ, TNF-α, IL-4, IL-10) measured via ELISA in samples collected during summer and winter.
- Multilevel mixed-effects linear regression used to identify cytokine predictors.
- Survival analysis employed to assess relapse predictors.
Main Results:
- Elevated IFN-γ levels correlated with increased MS relapse risk.
- Elevated TNF-α levels correlated with decreased MS relapse risk, an effect dependent on IFN-γ levels.
- The association of IFN-γ with relapse risk was diminished by immunomodulatory therapies, summer season, and higher vitamin D levels.
- The inverse association of TNF-α with relapse risk was observed under similar conditions (treatment, season, vitamin D) and in individuals with the wild-type TNFRSF1A SNP rs1800693.
- IL-4 and IL-10 showed no consistent association with relapse risk.
Conclusions:
- IFN-γ and TNF-α exhibit significant, context-dependent effects on MS relapse risk.
- Modulating factors include immunomodulatory therapies, season, serum vitamin D levels, and specific genetic variations (TNFRSF1A genotype).
- These findings highlight the role of altered immune cell reactivity in modulating MS disease activity.
