Vojnosanitetski pregled 2012 Volume 69, Issue 2, Pages: 151-156
https://doi.org/10.2298/VSP1202151O
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Tumor necrosis factor-alfa and interleukin-4 in cerbrospinal fluid and plasma in different clinical forms of multiple sclerosis
Obradović Dragana (Military Medical Academy, Clinic for Neurology, Belgrade)
Kataranovski Milena (Military Medical Academy, Institute for Medical Research, Belgrade)
Dinčić Evica (Military Medical Academy, Clinic for Neurology, Belgrade)
Obradović Slobodan (Military Medical Academy, Clinic for Emergency and Internal Medicine, Belgrade)
Čolić Miodrag (Military Medical Academy, Institute for Medical Research, Belgrade)
Background/Aim. Multiple sclerosis (MS) is an immunemediated central nervous
system disease characterized by inflammation, demyelination and axonal
degeneration. Cytokines are proven mediators of immunological process in MS.
The aim of this study was to investigate whether there is a difference in
the production of the tumor necrosis factor alpha (TNF-alpha) and
interleukin-4 (IL-4) in cerebrospinal fluid (CSF) and plasma in the MS
patients and the controls (other neurological non-inflammatory diseases) and
to determine a possible difference in these cytokines in plasma and CSF in
different clinical forms of MS. Methods. This study involved 60 consecutive
MS patients - 48 patients with relapsing-remitting MS (RRMS) and 12 patients
with secondary progressive MS (SPMS). The control group consisted of 20, age
and sex matched, nonimmunological, neurological patients. According to the
clinical presentation of MS at the time of this investigation, 34 (56.7%)
patients had relapse (RRMS), 14 (23.3%) were in remission (RRMS), while the
rest of the patients, 12 (20.0%), were SPMS. TNF-alpha and IL-4
concentrations were measured in the same time in CSF and plasma in the MS
patients and the controls. Extended disability status score (EDSS), albumin
ratio and IgG index were determined in all MS patients. Results. The MS
patients had significantly higher CSF and plasma levels of TNF-alpha than
the controls (p < 0.001 for both samples). IL-4 CSF levels were
significantly lower in the MS patients than in the controls (p < 0.001),
however plasma levels were similar. The patients in relapse (RRMS) and with
progressive disease (SPMS) had higher concentrations of CSF TNF-alpha levels
than the patients in remission (p < 0.001). IL-4 CSF levels in relapse
(RRMS) and SPMS groups were lower than in the patients in remission. The
patients in remission had an unmeasurable plasma TNF-alpha level and the
patients with SPMS had significantly lower IL-4 levels in plasma than the
patients in relapse and remission (p < 0.001). The only significant
correlation between cytokine level with either EDSS, or albumin ratio, or
IgG index, was found between CSF TNF-alpha levels and albumin ratio in the
patients with relapse (R square = 0.431, p < 0.001). Conclusion. According
to the obtained data MS relapse was characterized by high concentrations of
TNF-alpha in CSF and plasma and low concentrations of IL-4 in CSF. Remission
was characterized by high concentrations of IL-4 and low concentrations of
TNF-alpha both in CSF and plasma. SPMS was characterized with lower
concentrations of TNF-alpha and IL-4 compared to relapse, both in CSF and
plasma.
Keywords: multiple sclerosis, tumor necrosis factor-alpha, interleukin-4, plasma, cerebrospinal fluid, disease progression, treatment outcome