Assessment of Interleukin-17A, Interleukin-10 and Transforming Growth Factor-Beta1 Serum Titers in Relapsing Remitting Multiple Sclerosis Patients Treated with Avonex, Possible Biomarkers for Treatment Response.
BACKGROUND
Individual response to interferon beta (IFN-β) 1a treatment is heterogeneous in multiple sclerosis (MS). Our objective was to find a connection between serum levels of interleukin (IL)-10, IL-17 and transforming growth factor beta (TGF-β)1 in MS patients treated with IFN-β in order to identify the nonresponders (NR).


METHODS
We included in the study 32 healthy subjects and 32 MS patients: 10 naive, 10 early treated and 12 late treated with INF-β1a. Serum determination of cytokines and brain MRI were performed at the beginning of the study, after 6 and 12 months. Rio score was calculated at the end of the study.


RESULTS
MS patients had initially a significant higher level of IL-17 and a lower level of TGF-β1 compared to healthy subjects. IL-17 level in early treated patients was significantly lower compared to the naive and late treated groups. INF-β1a treatment significantly increased IL-10 and decreased IL-17 levels. Initial low levels of IL-10 were associated with an increase in physical disability. IL-17 levels positively correlated with the number of relapses and MRI activity. Nine patients were NR to Avonex. Patients with a Rio score of 3 had higher initial levels of IL-17 and those with a Rio score of 0 had higher initial levels of IL-10 and TGF-β1.


CONCLUSIONS
IFN-β1a decreased IL-17 and increased IL-10 seric levels; IL-17 significantly correlated with MS activity; TGF-β1 activity is titer-dependent, increased levels were associated with IL-17 inhibition; NR patients to IFN-β1a will have initial high IL-17 and low IL-10 and TGF-β seric levels.
Rodica
R
Balasa
University of Medicine and Pharmacy Targu Mures, Department of Neurology, Targu Mures, Romania, Gh Marinescu 50, 540136,. Romania.
Smaranda
S
Maier
Septimiu
S
Voidazan
Adina
A
Hutanu
Zoltan
Z
Bajko
Anca
A
Motataianu
Brandusa
B
Tilea
Cristina
C
Tiu
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging; D016207:Cytokines / Q000097:blood; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood*; D020381:Interleukin-17 / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011446:Prospective Studies; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; C508609:IL10 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D000068556:Interferon beta-1a
Avonex; Interferon beta; disease modifying therapies; interleukin-10; interleukin-17A; multiple sclerosis; transforming growth factor-beta1.