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Updated: Feb 5, 2026
A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data
Published on: December 9, 2015
Prophylactic treatment against GM-CSF, but not IL-17, abolishes relapses in a chronic murine model of multiple
Catherine Uyttenhove1,2, Mélanie Gaignage1,2, Dominique Donckers1,2
1Ludwig Cancer Research, Brussels Branch, Brussels, Belgium.
Abstract:
The pathogenic role of IL-17 and GM-CSF has been unravelled in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). However, in most models, EAE is characterised by a monophasic attack which is not representative of the relapsing nature nor the chronicity displayed in MS. Here, we used proteolipid protein peptide (PLP139-151 ) to trigger EAE-relapses (EAE-II) in SJL mice that had recovered from a primary-EAE episode (EAE-I). This procedure resulted in severe and irreversible disease that, unlike EAE-I, was not abolished by anti-IL-17-mAb. In contrast, prophylactic anti-GM-CSF-mAb treatment prevented EAE-I and -II. Strikingly, the expression of T-cell transcription factors and cytokines/chemokines in mice treated with anti-GM-CSF during both EAE episodes was silenced. Anti-GM-CSF-mAb treatment administered only during EAE-II did not completely prevent relapses but mice ultimately reached full recovery. Anti-GM-CSF treatment also strongly impaired and ultimately resolved monophasic MOG35-55 -induced EAE in C57Bl/6 mice. In such protected mice, anti-GM-CSF treatment also prevented a further relapse induced by MOG-revaccination. These results underscore the critical role of GM-CSF on pro-inflammatory mediator production. Furthermore, we observed a strong preventive and curative effect of anti-GM-CSF neutralisation in two EAE models, relapsing and chronic. Altogether these findings are relevant for further MS research.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Anti-GM-CSF treatment effectively prevented and resolved both relapsing and chronic EAE in mice.
Area of Science:
- Neuroimmunology
- Immunology
- Experimental Neurology
Background:
- The pathogenic roles of Interleukin-17 (IL-17) and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) are established in experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis (MS).
- Existing EAE models often display monophasic attacks, failing to replicate the relapsing-remitting and chronic disease courses observed in MS patients.
Purpose of the Study:
- To investigate the efficacy of anti-GM-CSF monoclonal antibody (mAb) treatment in a relapsing-remitting EAE model that mimics chronic MS.
- To evaluate the impact of GM-CSF neutralization on pro-inflammatory mediator production and disease progression in different EAE models.
Main Methods:
- Induction of relapsing EAE (EAE-II) in SJL mice using proteolipid protein peptide (PLP139-151) after recovery from primary EAE (EAE-I).
- Treatment with anti-IL-17-mAb and anti-GM-CSF-mAb during different phases of EAE (EAE-I and EAE-II).
- Assessment of disease severity, relapse prevention, and recovery in treated mice; analysis of T-cell transcription factors, cytokines, and chemokines.
Main Results:
- Anti-IL-17-mAb failed to prevent severe, irreversible relapses in the EAE-II model, unlike in EAE-I.
- Prophylactic anti-GM-CSF-mAb treatment prevented both EAE-I and EAE-II, silencing key T-cell transcription factors and inflammatory mediators.
- Anti-GM-CSF-mAb treatment during EAE-II mitigated relapses and promoted full recovery, also resolving monophasic EAE and preventing further relapses upon re-vaccination in C57Bl/6 mice.
Conclusions:
- GM-CSF is a critical mediator of pro-inflammatory cytokine and chemokine production in EAE.
- Anti-GM-CSF neutralization demonstrates significant preventive and curative potential in both relapsing and chronic EAE models.
- These findings highlight GM-CSF as a promising therapeutic target for progressive forms of multiple sclerosis.
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