The analysis of IL-1 beta and its naturally occurring inhibitors in multiple sclerosis: The elevation of IL-1 receptor antagonist and IL-1 receptor type II after steroid therapy

Dujmović, Irena; Mangano, Katia; Gazibara, Tatjana; Quattrocchi, Cinzia; Mesaroš, Šarlota; Stojsavljević, Nebojša; Nicoletti, Ferdinando; Drulović, Jelena

doi:10.1016/j.jneuroim.2008.11.004

Cited by 76 publications

(61 citation statements)

References 37 publications

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“…In consistence with previous reports, our results demonstrate increased IL-l beta levels in the sera of MS patients (24). This might potentially contribute to CNS damage in MS by different mechanisms.…”

Section: Tnf-a: Tumor Necrosis Factor-alpha; !L-lj3: Interleukin-l Bsupporting

confidence: 92%

Visfatin/NAMPT/PBCEF and Cytokine Concentration in Multiple Sclerosis Patients Compared to Healthy Subjects

et al. 2011

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The aim of the study is to measure IL-1 β, TNF-α, hs-CRP levels and Nampt/visfatin/PBCEF concentrations in patients with multiple sclerosis and to compare them with those of healthy control subjects. In a case-control study a total number of 192 people were recruited. Ninety-six of them were suffering from multiple sclerosis, age 34.80±8.75 years (mean±SD), who were referred form the Iranian Multiple Sclerosis Society. They included relapsing remitting (82 subjects) and both primary and secondary progressive (14 subjects) types of MS. The diagnosis was made according to the diagnostic criteria by a neurology consultant. Ninety-six healthy individuals were recruited from the Iranian Multicenter Osteoporosis Study (IMOS) as the control group. Following an overnight fasting, peripheral blood was taken from all subjects and centrifuged in order to separate serum for measurement of serum visfatin, Interleukin-1beta (IL-1β), TNF-α, and hs-CRP concentrations. Fat tissue mass was measured using DXA. Levels of visfatin, TNF-α and hs-CRP were significantly higher in MS patients. Besides, significant correlation was found between visfatin levels and those of TNF-α, IL-1β, hs-CRP in MS patients. Regarding the control group, significant correlation was found between visfatin levels and levels of TNF-α. However, we did not find any significant correlation between fat tissue mass and visfatin, TNF-α, IL-1β or hs-CRP levels in the MS group. However, there was a significant correlation between fat tissue mass and TNF-α level in the study population. Our findings demonstrated that proinflammatory factor levels were, although not significantly, higher in RRMS patients compared to PPMS and SPMS patients. The results suggest that levels of visfatin and pro-inflammatory cytokines are higher in MS patients compared to healthy subjects. Their higher levels may be, in part, attributable to the MS phenotypes independent of fat mass in patients. We believe that these results may shed some light on a potentially novel source of visfatin as well as explaining its regulating role in the inflammation process.

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Section: Tnf-a: Tumor Necrosis Factor-alpha; !L-lj3: Interleukin-l Bsupporting

confidence: 92%

Visfatin/NAMPT/PBCEF and Cytokine Concentration in Multiple Sclerosis Patients Compared to Healthy Subjects

et al. 2011

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“…Conversely, we found a decrease in the intrathecal IL-1Ra and IL-4 levels, and, together, these data demonstrate evidence for an activated IL-1 system not only in the joints, but also in the CNS of RA patients. Notably, although no RA patient in the present study had any clinical signs of neurological involvement, CSF levels of IL-1β were in the same range as previously detected in the active phase of MS (22). How, then, does peripheral inflammation result in the up-regulation of IL-1β production in the CNS?…”

Section: Discussionsupporting

confidence: 69%

“…MS is associated with cerebral immune and cytokine activation (1), and IL-1β release is prominent (22). Our study showed that IL-1β levels were markedly lower in MS patients in stable nonactive phase (median 0.54 pg/mL) ( Fig.…”

mentioning

confidence: 56%

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Lampa

Westman

Kadetoff

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

135

103

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During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1β concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1β, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments.

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“…Also, mononuclear cells from FMF patients release higher levels of IL-1β [8]. Moreover, a recent study by Yildirim et al [22] confirmed the presence of increased IL-1β levels in FMF patients during attack-free period. It has been shown that innate production of IL-1β is a risk factor for susceptibility and progression of relapse-onset MS [23].…”

Section: Discussionmentioning

confidence: 82%

The Potential Negative Effects of Interleukin-1β in Multiple Sclerosis Patients with MEFV Mutation

Alpaycı¹

2014

Ann Clin Anal Med

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ÖzetMEditerranean FeVer (MEFV) gen mutasyonlu multipl skleroz hastaları, bu mutasyonu taşımayanlara kıyasla daha hızlı ilerleyen hastalığa sahiptirler.Ancak, bunun mekanizması henüz tam olarak aydınlatılamamıştır. Bu yazı, bu hızlı ilerlemeden sorumlu olabilen interlökin-1β (IL-1β)'nın muhtemel rolünü önermektedir. MEFV geni, pyrin proteinini kodlar ve mutasyonları ailesel Akdeniz ateşine neden olur. MEFV mutasyonları, pyrin fonksiyonunun ortaya çıkmasına yol açar ve IL-1β'nın uygun olmayan salınımıyla sonuçlanır. gene mutation, have faster progression than the non-carriers. However, its underlying mechanism is not well understood. This article proposes the potential role of interleukin-1β (IL-1β) that may be responsible for this rapid progression. Mutations in MEFV, the gene encoding for protein pyrin, cause familial Mediterranean fever, lead to gain of pyrin function, resulting in inappropriate IL-1β release. Interleukin-1β is a major mediator of systemic inflammation and fever, and also it contributes to permeability of the bloodbrain barrier in active lesions of multiple sclerosis. Moreover, IL-1β promotes apoptosis of neurons and oligodendrocytes that produce the myelin sheath, which insulates axons. Thus, inflammatory damage, the blood-brain barrier disfunction, effects of fever on the central nervous system (or Uhthoff's phenomenon), and apoptosis of neurons and oligodendrocytes, which play an important role in the pathogenesis and clinical course of multiple sclerosis, can be induced by increased activation and release of IL-1β in the presence of MEFV gene mutations. Therefore, screening for MEFV mutations in patients with multiple sclerosis and treatment planning with IL-1β targeting drugs for the carriers, may be a logical idea that will be a source of inspiration for scientific studies.

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The analysis of IL-1 beta and its naturally occurring inhibitors in multiple sclerosis: The elevation of IL-1 receptor antagonist and IL-1 receptor type II after steroid therapy

Cited by 76 publications

References 37 publications

Visfatin/NAMPT/PBCEF and Cytokine Concentration in Multiple Sclerosis Patients Compared to Healthy Subjects

Visfatin/NAMPT/PBCEF and Cytokine Concentration in Multiple Sclerosis Patients Compared to Healthy Subjects

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

The Potential Negative Effects of Interleukin-1β in Multiple Sclerosis Patients with MEFV Mutation

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