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Induction of sTNF-R1 and sTNF-R2 by interferon beta-1b in correlation with clinical and MRI activity
C Laske1, P Oschmann, J Tofighi
1Department of Neurology, Justus-Liebig Univ, Giessen, Germany.
Objectives:
To investigate the influence of interferon (IFN) beta-1b on the serum levels of sTNF-R1, sTNF-R2 and TNF-beta in patients with multiple sclerosis (MS) in correlation with clinical and MRI activity.
Materials And Methods:
Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-lb every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine levels were measured by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease of every patient.
Results:
In the treatment group we found an obvious increase of sTNFR1 and sTNF-R2 (P < 0.001) and relatively stable serum levels of TNFbeta with no statistical significance (P = 0.56). In the control group, sTNF-R1 showed a significant decrease (P < 0.001) during the same observation period of 15 months. During the 15-month observation period, the MRI-responders group had significant larger mean AUC (area under the concentration-time curve) values of sTNF-R1 (P = 0.04) and sTNF-R2 (P = 0.01) when compared to the group of MRInonresponders.
Conclusion:
The present data suggest that IFN beta-1b induces the expression and shedding of TNF-R1 and TNF-R2. The magnitude of an increase of sTNF-Rs may be a marker for the effectiveness of treatment with IFN beta-1b.
Insights
Interferon beta-1b treatment for multiple sclerosis (MS) increased soluble tumor necrosis factor receptors (sTNF-Rs). Higher sTNF-R levels correlated with treatment effectiveness, suggesting they may serve as a biomarker for IFN beta-1b therapy.
Area of Science:
- Neuroimmunology
- Biochemistry
- Clinical Medicine
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Tumor necrosis factor (TNF) and its soluble receptors (sTNF-Rs) play a role in MS pathogenesis.
- Interferon beta-1b (IFN beta-1b) is an immunomodulatory therapy used for MS.
Purpose of the Study:
- To evaluate the effect of IFN beta-1b on serum levels of soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and TNF-beta in MS patients.
- To correlate these cytokine levels with clinical and magnetic resonance imaging (MRI) activity in MS patients.
Main Methods:
- A 15-month observational study involving 24 MS patients treated with IFN beta-1b and 21 untreated controls.
- Serum samples collected quarterly and analyzed for cytokine levels using ELISA.
- Cranial MRI performed biannually to assess disease burden.
Main Results:
- IFN beta-1b treatment significantly increased serum sTNF-R1 and sTNF-R2 levels (P < 0.001).
- Serum TNF-beta levels remained stable in the treatment group (P = 0.56).
- In controls, sTNF-R1 levels significantly decreased (P < 0.001).
- Higher mean area under the concentration-time curve (AUC) for sTNF-R1 and sTNF-R2 was observed in MRI-responders compared to non-responders.
Conclusions:
- IFN beta-1b treatment appears to induce the expression and shedding of TNF-R1 and TNF-R2.
- The increase in sTNF-Rs may serve as a potential biomarker for the efficacy of IFN beta-1b treatment in MS.
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