Multiple sclerosis (MS) is a progressive immune- mediated disease caused by demyelination of the central nervous system. Cytokines and their receptors have an important role in the evolution of MS lesions, and pro- and anti-inflammatory cytokine levels have been found to correlate with changes in MS disease activity. The aims of the present study were to evaluate the pro-inflammatory [tumor necrosis factor (TNF)-α and interleukin (IL) -1β, -6 and -12], T helper (Th) 1 [interferon (IFN)-γ], Th17 (IL-17) and Th2 (IL-4 and -10) cytokine serum levels in relapsing-remitting (RR)-MS patients and to evaluate the association between the cytokine profile and the progression and activity of the disease. Serum cytokine levels were assessed using enzyme linked-immunosorbent assays in 169 RR-MS patients in the remission clinical phase and 132 healthy individuals who were age-, gender-, ethnicity- and body mass index-matched. Disability and activity of the disease were evaluated using the Expanded Disability Status Scale and magnetic resonance imaging with gadolinium, respectively. IFN-γ and IL-6, -12 and -4 levels were higher in RR-MS patients compared to controls (P=0.0009, 0.0114, 0.0297 and 0.0004, respectively). IL-1 levels were higher in controls compared with RR-MS patients. IL-4 levels were higher in RR-MS patients with mild disability compared to those with moderate and severe disability (P=0.0375). TNF-α and IL-10 levels were higher in RR-MS patients with inactive disease compared with those with active disease. IL-17 levels showed a trend towards being higher in RR-MS patients with inactive disease compared to those with active disease (P=0.0631). Low TNF-α and high IFN-γ levels were independently associated with RR-MS (P=0.0078 and 0.0056, respectively) and also with the activity of the disease (P=0.0348 and 0.0133, respectively). Results indicated that RR-MS patients, even in the remission clinical phase, exhibit a complex system of inflammatory and anti-inflammatory cytokines that may interact to modulate the progression and activity of the disease.
Multiple sclerosis (MS) is a progressive immune-mediated disease caused by demyelination of the central nervous system (CNS), with perivascular infiltrates of autoreactive T-cells that recognize and react against autoantigens, including myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocytic glycoprotein (MOG) and myelin-associated glycoprotein (
MS is considered a T helper (Th) 1 lymphocyte-mediated disorder as levels of Th1-related molecules are increased in MS, however, the causes of the disease remain unclear. Th1 lymphocyte cells producing interferon (IFN)-γ and tumor necrosis factor (TNF)-α have been found in the perivascular infiltrates of MS patients (
Cytokines have been identified as major regulators of the immune system and attempts have been made to correlate cytokine levels with MS disease activity, assessed using magnetic resonance imaging (MRI). There is evidence that acute dysregulation of the balance of cytokines is one of the key factors during acute relapse, leading to acute inflammatory lesions in MS patients. Elevated serum and CSF TNF-α and -β levels have been associated with onset of MS relapse (
The clinical disability of MS patients is evaluated using the Expanded Disability Status Scale (EDSS) (
Cytokine changes have been investigated in MS patients from various populations worldwide. The majority of the studies enrolled a limited number of MS patients with various clinical forms of the disease during the remission or relapse phase (
The case-controlled study was approved by the Institutional Research Ethics Committee of the State University of Londrina (Paraná, Brazil) according to the 1964 Declaration of Helsinki and its later amendments. Voluntary written consent was obtained from all individuals prior to the start of the study. The study enrolled 169 consecutive RR-MS patients from the Neurology Outpatients Service of the Outpatient Clinic Hospital, State University of Londrina (Paraná, Brazil), during 2011. RR-MS patients were diagnosed according to the revised McDonald Criteria (
RR-MS patients and control subjects were age-, gender-, ethnicity- and body mass index (BMI)-controlled. Anthropometric measurements were obtained by body weight, measured to the nearest 0.1 kg using an electronic scale, with individuals wearing light clothing and no shoes. Height was measured to the nearest 0.1 cm using a stadiometer. BMI was calculated as weight (kg) divided by height (m) squared.
Blood samples for cytokine analysis were collected at the time of patient enrollment. The serum samples of MS patients were immediately separated, divided into aliquots and stored in a -80°C freezer for subsequent analysis, as described previously (
A database was created using the Excel Program of Microsoft Office and statistical analysis was performed using Graph Pad Prism v5.0 (Graph Pad Software, La Jolla, CA, USA). Categorical variables were analyzed using a Chi-square test (or Fisher's Exact test where appropriate) and were expressed in absolute number and percentage. Continuous variables were analyzed using the Mann-Whitney test and were expressed as the median, interquartile range (IQR; 25–75%) and range. Continuous variables of two groups or more were compared using the Kruskal-Wallis test with Dunn's post test. P<0.05 was considered to indicate a statistically significant difference. To determine which factors were independently associated with RR-MS, variables that presented P<0.20 in the univariate analyses and values with supposed clinical relevance or previous data in the literature were included in the multivariate logistic regression model. The multivariate analyses were evaluated using GraphPad Instat v3.0 (Graph Pad Software).
Demographic and anthropometric characteristics of the RR-MS patients and healthy individuals are shown in
Serum cytokine levels were compared between RR-MS patients and controls (
In the Th1 cytokine profile, IFN-γ levels were higher among RR-MS patients compared with controls (P=0.0009). However, the Th17 cytokine IL-17 did not differ between RR-MS and controls (P=0.2298).
Th2 anti-inflammatory cytokine profile results revealed that IL-4 levels were higher in RR-MS patients compared with controls (P=0.0004). Although IL-10 levels were higher in RR-MS patients compared with controls, this difference was not considered significant (P=0.1901).
Logistic regression analysis of the results obtained from 169 RR-MS patients and 132 controls included the variables IL-1, -6, -12, -4 and-10, TNF-α and IFN-γ and demonstrated that low TNF-α and high IFN-γ levels were independently associated with RR-MS (P=0.0078 and 0.0056, respectively).
Serum cytokine levels were also evaluated according to the disability of RR-MS patients using categorized EDSS scores in mild, moderate and severe disability (
Serum IL-1 levels did not differ according to the disability exhibited by the RR-MS patients (P=0.4422). Although IL-6, TNF-α and IFN-γ levels were higher among the RR-MS patients with severe disability compared with those observed among the RR-MS patients with moderate and mild disability, the difference was not significant (P=0.7408, 0.6896 and 0.6032, respectively). No significant difference was found in IL-12 and -17 levels obtained among the RR-MS patients with mild, moderate and severe disability (P=0.5083 and 0.2359, respectively). Higher IL-4 levels were observed among RR-MS patients with mild disability compared with moderate and severe disability (P=0.0375). However, no difference was observed in IL-10 levels with respect to patient disability (P=0.8680). Following logistic regression analysis, variables presented no independent association with disease disability (P>0.05).
Serum cytokine levels obtained from RR-MS patients were also evaluated according to the disease activity assessed by Gd-enhancing lesions observed during MRI (
No difference was detected in IL-1, -6, -12 and -4 levels between RR-MS patients with positive and negative Gd-enhancing lesions (P=0.4752, 0.1129, 0.9089 and 0.8980, respectively). Although IFN-γ levels were higher among RR-MS patients presenting positive Gd-enhancing lesions compared with negative ones, no difference was found by univariate analysis (P=0.1643). TNF-α levels were higher in patients with negative Gd-enhancing lesions than positive (P=0.0572). Serum IL 17 levels showed a growing trend towards being higher in RR MS patients with inactive disease compared to those with active disease (P=0.0631). While serum IL-10 levels were higher among RR-MS patients with negative Gd-enhancing lesions than those with positive (P=0.0533). IL-4 levels did not differ between these patients (P=0.8980).
Logistic regression analysis between the results obtained from RR-MS patients and the disease activity, including the variables age, TNF-α, IFN-γ and IL-6, -17 and -10, demonstrated that low TNF-α and high IFN-γ levels were independently associated with disease activity (P=0.0348 and 0.0133, respectively).
The present study evaluated the serum cytokine profile exhibited by RR-MS patients in a remission clinical phase from a population from South Brazil. Theoretically, CSF may reflect the relevant inflammatory process to a higher degree compared with other samples, due to its proximity to inflammatory lesions in the CNS. However, due to the flow pattern of CSF, it is unlikely that CSF in the lumbar cistern accurately reflects the production of inflammatory markers in the supratentorial region, where the majority of MS-related inflammation occurs (
To obtain more homogeneity of the cohort, only patients with the RR-MS clinical form were included in this study. The main result obtained in this study was elevated serum IFN-γ and IL-6, -12 and -4 levels in RR-MS patients compared with controls. MS patients with mild EDSS presented elevated IL-4 levels. RR-MS patients with inactive disease exhibited elevated levels of TNF-α and IL-10 and -17. Logistic regression analysis revealed that low TNF-α and high IFN-γ levels were associated with MS and disease activity.
The demographic and clinical characteristics exhibited by the RR-MS patients are consistent with those of previous studies (
RR-MS patients and controls were age-, gender-, ethnicity- and BMI-matched for cytokine analysis. These parameters were controlled to minimize their effect of them on serum cytokine levels (
The increased IL-6 levels identified among RR-MS patients compared with controls are consistent with previous studies. One study demonstrated that the number of IL-6 mRNA expressing mononuclear cells was enriched in CSF of MS patients (
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TNF-α levels were lower in RR-MS patients than the controls, as demonstrated by the multivariate analysis. This result is consistent with previous studies reporting lower TNF-α levels in MS patients compared with controls (
In the present study, increased IFN-γ levels obtained among MS patients compared with controls were also consistent with previous studies. Lymphocytes producing IFN-γ were identified in the perivascular infiltrates of MS patients (
Although IL-17 expression has been demonstrated to generate a highly pro-inflammatory environment and to induce severe pathological conditions (
The RR-MS patients enrolled in this study presented high levels of IL-12 which, in turn, antagonized IL-17 production and by this effect, reduced IL-1β- and TNF-α-induced production by IL-17. In addition to the consumption of TNF-α in CNS lesions, the reduced production may explain, in part, why TNF-α levels did not differ among the patients and controls (
The higher IL-12 levels exhibited by RR-MS patients compared with controls enrolled in the present study are also consistent with previous observations that IL-12 levels were upregulated in MS patients (
In the Brazilian cohort enrolled in the present study, higher levels of IL-4 were found in MS patients compared with controls, a result consistent with previous studies (
Although IL-10 levels were higher in MS patients compared with controls, no statistically significant difference was found. It was previously suggested that IL-10 is important for recovery of EAE (
The cytokine profile was also evaluated according to the EDSS of the RR-MS patients. Patients with mild disability were younger than those with moderate and severe disability, a result that was expected since at the beginning of the disease, low EDSS scores are detected among RR-MS patients and disability increases during disease progression (
In addition, serum IL-17 and -10 did not differ between EDSS categories. Several studies have reported that differential production of IL-10 may be a factor in the severity of MS (
It was not possible to control age of RR-MS patients with regards to disease activity. However, logistic regression analysis revealed that age did not affect cytokine levels. There is evidence that an acute deregulation in the balance of cytokines is one of the key factors during an acute relapse leading to acute inflammatory lesions. RR-MS patients with active disease presented with lower TNF-α and higher IFN-γ levels compared with RR-MS patients without active disease, as demonstrated by multivariate analysis. IFN-γ and IL-12 levels were increased in brain, CSF or peripheral blood from MS patients, particularly during acute exacerbation phases (
Cytokines only function when bound to membrane receptors and the TNF-α receptor is present in almost all cells (
Although IL-6 levels were higher in RR-MS patients with inactive disease, this difference was not identified to be statistically significant. This result is in agreement with a previous study (
A previous study has demonstrated that serum IL-12 levels correlate with active lesions (
Increased levels of IL-17 were found in RR-MS patients with inactive disease. Th17 cell differentiation is orchestrated by multiple cytokines, including TGF-β and IL-6, -1-β, -21 and -23 (stimulating) and IFN-γ and IL-4, -12, -10 and -27 (inhibiting). The Th17 cell is a recently identified cell lineage that has been hypothesized to be critical for the development of the autoimmune response, in addition to Th1 cells (
Serum IL-4 levels did not differ between RR-MS patients with active and inactive disease and this result was not consistent with previous studies that demonstrated high IL-4 levels in acute and chronic lesions (
Previously, Cannella and Raine (
The present study demonstrates that RR-MS patients exhibit a complex system of cytokines which interact to modulate disease activity and the disabilities associated with it. Even in the remission phase of the disease and under immunomodulatory therapy, RR-MS patients present with an imbalance between pro-inflammatory, Th1, -2 and -17 cytokines. TNF-α was observed to be consumed in CNS lesions and activation of the cellular immune response was mediated by high levels of IFN-γ. These results are likely to contribute to an improved understanding of the role of the cytokine profile in RR-MS and may aid the development of new neuroprotective and neurorestorative therapeutic strategies.
The present study was supported by grants from the Coordination for the Improvement of Higher Level of Education Personnel of Brazilian Ministry of Education, Institutional Program for Scientific Initiation Scholarship of the National Council for Scientific and Technological Development, State University of Londrina and Bayer HealthCare. The authors thank the State University of Londrina and HUTec Foundation for technical and administrative support.
Demographic and anthropometric characteristics of RR-MS patients and healthy controls in a population from South Brazil.
Characteristics | RR-MS patients (n=169) | Healthy controls (n=132) | P-value |
---|---|---|---|
Gender, n (%) | |||
Female | 123 (72.8) | 104 (78.8) | 0.2298 |
Male | 46 (27.2) | 28 (21.2) | |
Ethnicity, n (%) | |||
Caucasian | 144 (85.2) | 106 (80.3) | 0.2604 |
Non-Caucasian | 25 (14.8) | 26 (19.7) | |
Age, years | |||
Median (IQR) | 42.0 (30.0–51.5) | 38.5 (32.0–46.7) | 0.1090 |
Range | 14.0–85.0 | 26.0–62.0 | |
BMI, kg/m2 | |||
Median (IQR) | 23.5 (21.5–27.2) | 24.8 (22.0–27.9) | 0.1120 |
Range | 16.9–44.0 | 16.4–40.2 |
Chi-square test (P<0.05).
Mann Whitney test (P<0.05).
RR-MS, relapsing-remitting multiple sclerosis; BMI, body mass index; IQR, interquartile range.
Clinical characteristics of RR-MS in a population from South Brazil.
Clinical characteristics | n | RR-MS patients |
---|---|---|
Age at onset, years | 169 | |
Median (IQR) | 33.0 (24.5–44.0) | |
Range | 10.0–68.0 | |
Disease duration, years | 169 | |
Median (IQR) | 7.0 (3.0–10.0) | |
Range | 0.0–52.0 | |
EDSS, n (%) | 146 | |
Mild (0.0–4.0) | 113 (77.2) | |
Moderate (4.5–5.5) | 20 (13.8) | |
Severe (6.0–10.0) | 13 (9.0) | |
Lesion location at MRI, n (%) | 161 | |
Brain white matter | 130 (80.8) | |
Spinal cord | 54 (33.5) | |
Optic nerve | 18 (11.2) | |
Disease activity at MRI, n (%) | 161 | |
Positive Gd-enhancing lesions | 35 (21.7) | |
Negative Gd-enhancing lesions | 126 (78.3) | |
RR-MS treatment, n (%) | 156 | |
IFN-β1a | 37 (23.7) | |
IFN-β1b | 81 (51.9) | |
Glatiramer acetate | 21 (13.5) | |
Natalizumab | 03 (1.9) | |
Treatment naïve | 05 (3.2) | |
No adhesion | 09 (5.8) | |
Corticosteroids (mg/day) | 18 (10.7) |
RR-MS, relapsing-remitting multiple sclerosis; BMI, body mass index; EDSS, Expanded Disability Status Scale; MRI, magnetic resonance imaging; IQR, interquartile range; IFN, interferon; Gd, gadolinium.
Serum cytokine levels obtained from RR-MS patients and healthy controls in a population from South Brazil.
Cytokine | RR-MS (n=169) | Healthy controls (n=132) | P-value |
---|---|---|---|
IL-1β (pg/ml) | |||
Median (IQR) | 2.0 (2.0–2.5) | 2.0 (2.0–4.5) | 0.0992 |
Range | 2.0–40.7 | 2.0–63.2 | |
IL-6 (pg/ml) | |||
Median (IQR) | 1.9 (1.0–3.9) | 1.1 (1.0–3.4) | 0.0114 |
Range | 1.0–158.0 | 1.0–49.5 | |
TNF-α (pg/ml) | |||
Median (IQR) | 2.0 (2.0–4.3) | 2.0 (2.0–11.2) | 0.1840 |
Range | 2.0–68.4 | 2.0–384.5 | |
IL-12 (pg/ml) | |||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–2.0) | 0.0297 |
Range | 2.0–93.7 | 2.0–31.1 | |
IFN-γ (pg/ml) | |||
Median (IQR) | 42.6 (23.4–74.9) | 24.8 (11.7–80.8) | 0.0009 |
Range | 2.0–500.0 | 2.0–476.7 | |
IL-17 (pg/ml) | |||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–2.0) | 0.2298 |
Range | 2.0–53.2 | 2.0–88.2 | |
IL-4 (pg/ml) | |||
Median (IQR) | 1.0 (1.0–4.0) | 1.0 (1.0–1.0) | 0.0004 |
Range | 1.0–26.4 | 1.0–16.1 | |
IL-10 (pg/ml) | |||
Median (IQR) | 4.7 (3.3–6.5) | 4.0 (2.9–5.6) | 0.1901 |
Range | 1.0–104.9 | 1.0–28.2 |
Mann Whitney test (P<0.05).
RR-MS, relapsing-remitting multiple sclerosis; IL, interleukin; TNF-α, tumor necrosis factor α; IFN- γ, interferon γ; IQR, interquartile range.
Serum cytokine levels obtained from RR-MS patients, according to the EDSS.
Characteristics | Mild EDSS | Moderate EDSS | Severe EDSS | P-value |
---|---|---|---|---|
MS patients, n | 146 | 113 | 13 | |
Range | (0.0–4.0) | (4.5–5.5) | (6.0–10.0) | |
Gender, n (%) | ||||
Female | 83 (56.9) | 16 (11.0) | 7 (4.8) | 0.2357 |
Male | 30 (20.5) | 4 (2.7) | 6 (4.1) | |
Ethnicity, n (%) | ||||
Caucasian | 93(63.7) | 19 (13.0) | 10 (6.8) | 0.2933 |
Non-Caucasian | 20 (13.7) | 01 (0.7) | 03 (2.1) | |
Age, years | ||||
Median (IQR) | 39.0 (28.0–48.0) | 39.5 (34.3–56.0) | 52.0 (39.5–57.0) | 0.0034 |
Range | 14.0–79.0 | 24.0–85.0 | 29.0–71.0 | |
BMI, kg/m2 | ||||
Median (IQR) | 23.4 (21.7–27.4) | 24.8(20.5–27.3) | 20.9 (19.9–23.9) | 0.2998 |
Range | 17.5–44.0 | 16.9–33.6 | 19.8–24.6 | |
Corticosteroids, mg/day | ||||
Median (IQR) | 20.0 (20.0–20.0) | 25.0 (20.0–30.0) | 20.0 (20.0–20.0) | 0.4333 |
Range | 2.0–40.0 | 20.0–30.0 | 20.0–20.0 | |
IL-1β, pg/ml | ||||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–5.0) | 2.0 (2.0–2.0) | 0.4422 |
Range | 2.0–40.7 | 2.0–15.9 | 2.0–2.0 | |
IL-6, pg/ml | ||||
Median (IQR) | 1.8 (1.0–3.8) | 2.1 (1.0–3.9) | 3.9 (1.3–4.9) | 0.7408 |
Range | 1.0–122.3 | 1.0–158.0 | 1.0–5.6 | |
TNF-α, pg/ml | ||||
Median (IQR) | 2.0 (2.0–5.0) | 2.0 (2.0–3.3) | 2.7 (2.0–28.8) | 0.0572 |
Range | 2.0–50.1 | 2.0–4.7 | 2.0–30.0 | |
IL-12, pg/ml | ||||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–2.0) | 2.0 (2.0–4.5) | 0.5083 |
Range | 2.0–93.7 | 2.0–7.5 | 2.0–11.8 | |
INF-γ, pg/ml | ||||
Median (IQR) | 41.2 (19.6–77.7) | 55.5 (27.1–36.3) | 52.6 (36.3–72.0) | 0.6032 |
Range | 5.0–500.0 | 9.8–500.0 | 27.0–500.0 | |
IL-17, pg/ml | ||||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–2.0) | 2.0 (2.0–5.5) | 0.2359 |
Range | 2.0–53.2 | 2.0–4.2 | 2.0–13.7 | |
IL-4, pg/ml | ||||
Median (IQR) | 1.0 (1.0–9.6) | 1.0 (1.0–1.4) | 1.0 (1.0–1.0) | 0.0375 |
Range | 1.0–26.4 | 1.0–17.2 | 1.0–1.0 | |
IL-10, pg/ml | ||||
Median (IQR) | 4.6 (3.2–6.6) | 4.4 (3.4–6.8) | 5.0 (3.0–5.2) | 0.8680 |
Range | 1.0–21.9 | 2.2–16.5 | 2.9–5.4 |
Chi-square test (P<0.05).
Kruskal-Wallis test with Dunn's Post test (P<0.05).
Eighteen RR-MS patients were treated with corticosteroids at the time of enrollment in the study.
RR-MS, relapsing-remitting multiple sclerosis; EDSS, Expanded Disability Status Scale; IL, interleukin; TNF-α, tumor necrosis factor α; IFN- γ, interferon γ; IQR, interquartile range.
Serum cytokine levels obtained from RR-MS patients according to Gd-enhancing lesions assessed by MRI.
MRI | |||
---|---|---|---|
|
|||
Characteristics | Positive Gd | Negative Gd | P-value |
RR-MS patients, n | 35 | 126 | |
Gender, n (%) | |||
Female | 24 (14.9) | 93 (57.8) | 0.5383 |
Male | 11(6.8) | 33 (20.5) | |
Ethnicity, n (%) | |||
Caucasian | 29 (18.0) | 107 (66.5) | 0.7656 |
Non-Caucasian | 06 (3.7) | 107 (66.5) | |
Age, years | |||
Median (IQR) | 32.0 (27.0–44.0) | 44.0 (32.0–52.3) | 0.0032 |
Range | 14.0–79.0 | 15.0–85.0 | |
BMI, kg/m2 | |||
Median (IQR) | 23.4 (22.1–27.7) | 23.5 (21.1–27.1) | 0.6464 |
Range | 19.3–35.5 | 16.9–44.0 | |
Corticosteroids, mg/day | |||
Median (IQR) | 20.0 (20.0–20.0) | 20.0 (20.0–22.5) | 0.9029 |
Range | 20.0–40.0 | 5.0–30.0 | |
IL-1β, pg/ml | |||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–2.9) | 0.4752 |
Range | 2.0–18.0 | 2.0–40.7 | |
IL-6, pg/ml | |||
Median (IQR) | 1.3 (1.0–3.2) | 2.4 (1.0–4.0) | 0.1129 |
Range | 1.0–158.0 | 1.0–122.3 | |
TNF-α, pg/ml | |||
Median (IQR) | 2.0 (2.0–2.1) | 2.0 (2.0–5.6) | 0.0457 |
Range | 2.0–17.5 | 2.0–68.4 | |
IL-12, pg/ml | |||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–2.0) | 0.9089 |
Range | 2.0–48.3 | 2.0–93.7 | |
IFN-γ, pg/ml | |||
Median (IQR) | 52.8 (25.0–131.4) | 39.5 (23.0–70.7) | 0.1643 |
Range | 6.4–500.0 | 2.0–500.0 | |
IL-17, pg/ml | |||
Median (IQR) | 2.0 (2.0–2.0) | 2.0 (2.0–2.6) | 0.0631 |
Range | 2.0–15.6 | 2.0–53.2 | |
IL-4, pg/ml | |||
Median (IQR) | 1.0 (1.0–14.9) | 1.0 (1.0–4.1) | 0.8980 |
Range | 1.0–22.3 | 1.0–26.4 | |
IL-10, pg/ml | |||
Median (IQR) | 3.4 (2.3–5.8) | 4.9 (3.4–6.5) | 0.0533 |
Range | 1.0–15.9 | 1.0–104.9 |
Chi-square test (P<0.05).
Mann Whitney test (P<0.05).
Eighteen RR-MS patients were treated with corticosteroids at the time of enrollment in the study.
RR-MS, relapsing-remitting multiple sclerosis; BMI, body mass index; IL, interleukin; TNF-α, tumor necrosis factor α; IFN- γ, interferon γ; IQR, interquartile range; Gd, gadolinium.