Abstract:
Background: The balance between T helper cells Th2- and Th1-related cytokines plays a key role in multiple
sclerosis (MS). A shift from a Th1 towards a Th2 cytokine profile could have a beneficial effect on the clinical course
of the disease. The objective of this study was to assess Th2/Th1 cytokine profile in relapsing-remitting MS (RRMS)
patients receiving an immunosuppressive treatment with natalizumab (NAT), or an immunomodulatory treatment
with glatiramer acetate (GA) after one year of treatment.
Methods: This was an observational cross-sectional study. All consecutive patients diagnosed with RRMS who had
received GA or NAT for 12 months were included in the study. We determined serum levels of Th1 and Th2
cytokines (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, monocyte chemotactic protein
[MCP]-1, tumor-necrosis factor [TNF]-α, interferon [IFN]-γ and granulocyte macrophage colony stimulating factor
[GM-CSF]) by flow cytometry. Th2/Th1 bias was defined based on the ratio of IL-4, IL-5, IL-6 or IL-10 Th2 cytokines
and proinflammatory INF-γ or TNF-α Th1 cytokines.
Results: Eleven patients under treatment with NAT and 12 patients treated with GA were evaluated. RRMS patients
treated with NAT showed significantly higher levels of IL-6 (p < 0.05), MCP-1 (p < 0.01), and GM-CSF (p < 0.05)
compared to GA patients after one year of treatment. A trend for increasing of IL-12p70, IL-1b, TNF- α and IFN- γ
levels was also found in patients receiving NAT compared to GA patients. IL-4/IFN-γ, IFN-γ/TNF-α and IL-10/IFN-γ
ratios as markers of Th2/Th1 ratio were significantly elevated in GA patients compared to those receiving NAT
(p < 0.05).
Conclusion: In conclusion, our findings suggest that GA promotes a superior Th2-biased anti-inflammatory
response as compared with NAT in the systemic circulation of RRMS patients. Future studies with larger cohorts will
determine whether this immune Th2 shift in GA patients is associated with a beneficial effect on disease outcome