Alterations in serum MMP-8, MMP-9, IL-12p40 and IL-23 in multiple sclerosis patients treated with interferon-beta1b.
BACKGROUND
Interferon-beta1b (IFN-beta1b), an effective treatment for multiple sclerosis (MS), lessens disease severity in MS patients. However, the mechanisms of its immunoregulatory and anti-inflammatory effects in MS remain only partially understood. Matrix metalloproteinases (MMP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are involved in blood brain barrier disruption and formation of MS lesions. Th1/Th17 cytokines e.g. interleukins IL-12p40, IL-17, and IL-23, are associated with MS disease activity and are significant players in pathogenesis of MS.


OBJECTIVE
During a 1-year prospective study, we serially measured serum MMP-8, MMP-9, TIMP-1, IL-12p40, IL-17, and IL-23 in 24 patients with relapsing-remitting MS. We compared the results to clinical course and to brain magnetic resonance imaging. IFN-beta1b decreased serum MMP-8 and MMP-9 (not TIMP-1).


RESULTS
The sustained treatment with IFN-beta1b attenuated the pro-inflammatory environment by significantly reducing the serum IL-12p40, IL-23, and showed a trend for decreasing IL-17. Decreased serum MMP-8, MMP-9, IL-12 and IL-23 levels were correlated with a decrease in the number of contrast-enhanced T2-weighted lesions.


CONCLUSIONS
Early treatment of MS with IFN-beta1b may stabilize clinical disease by attenuating levels of inflammatory cytokines and MMPs. Serial measurement of inflammatory mediators may serve as sensitive markers to gauge therapeutic responses to IFN-beta1b during the first year of treatment.
Alexander
J S
JS
Departments of Molecular and Cellular Physiology, LSUHSC-Shreveport, LA 71130-3932, USA.
Harris
M K
MK
Wells
S R
SR
Mills
G
G
Chalamidas
K
K
Ganta
V C
VC
McGee
J
J
Jennings
M H
MH
Gonzalez-Toledo
E
E
Minagar
A
A
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D053762:Interleukin-12 Subunit p40 / Q000097:blood*; D020381:Interleukin-17 / Q000097:blood; D053759:Interleukin-23 / Q000097:blood*; D008145:Louisiana; D008279:Magnetic Resonance Imaging; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D011446:Prospective Studies; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; C500879:IL12B protein, human; D007155:Immunologic Factors; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D019715:Tissue Inhibitor of Metalloproteinase-1; D000068576:Interferon beta-1b; D016899:Interferon-beta; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9