Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis.
OBJECTIVE
Chronic and acute dysregulation of the cytokine network has been described in multiple sclerosis (MS). Inflammatory lesions in the central nervous system of MS patients can be assessed by brain magnetic resonance imaging (MRI). This study has been performed to investigate whether changes of cytokines correlate with morphological changes as determined by MRI.


METHODS
We included 46 patients with relapsing-remitting MS in the study. The serum concentrations of tumor necrosis factor-beta (TNF-beta), TNF receptor-1 (TNFR-1; 55 kDa) and TNFR-2 (75 kDa), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were measured by enzyme linked immunosorbent assay in all patients. Each parameter was correlated with clinical findings and brain MRI parameters. We measured both the number (lesion load) and cumulated area (disease burden) of all lesions on brain MRI. In addition, the number and cumulated area of those lesions showing signs of activity [Gadolinium (Gd)-enhancement, perifocal edema] were determined.


RESULTS
A non-significant trend (P < 0.05) was found only for the correlation of serum IFN-gamma levels and the number of active MRI lesions showing both Gd-enhancement and perifocal edema in the subgroup of patients (n=21) with active lesions. When corrected for multiple comparisons, this correlation was not significant anymore, as it was above the corrected P-value of 0.001. We could not observe any further correlation of cytokine levels and MRI parameters. However, TNF-beta serum levels were significantly (P < 0.05) elevated in the patient subgroups with higher number of lesions and disease burden, respectively.


CONCLUSIONS
Our data show that the determination of serum levels of the investigated cytokines and cytokine receptors is not useful as a tool to determine subclinical disease activity and severity as assessed by brain MRI.
Kraus
J
J
Department of Neurology, Research Group for Multiple Sclerosis and Neuroimmunology, Justus-Liebig University Giessen, Giessen, Germany. joerg.r.kraus@neuro.med.uni-giessen.de
Kuehne
B S
BS
Tofighi
J
J
Frielinghaus
P
P
Stolz
E
E
Blaes
F
F
Laske
C
C
Engelhardt
B
B
Traupe
H
H
Kaps
M
M
Oschmann
P
P
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008233:Lymphotoxin-alpha / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma