IL-6 detection in multiple sclerosis brain

Maimone, Davide; Guazzi, Gianni; Annunziata, Pasquale

doi:10.1016/s0022-510x(96)00283-3

Cited by 154 publications

(117 citation statements)

References 32 publications

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“…The importance of this pleiotropic cytokine in inflammatory demyelination is underscored by its high expression in the CNS (42) and, specifically, in MS lesions at sites of active demyelination (43). IL-6 is also one of few cytokines unconditionally required for the development of experimental autoimmune encephalomyelitis, an animal model of MS (44).…”

Section: Discussionmentioning

confidence: 99%

TLR2 Stimulation Regulates the Balance between Regulatory T Cell and Th17 Function: A Novel Mechanism of Reduced Regulatory T Cell Function in Multiple Sclerosis

Nyirenda

Morandi

Vinkemeier

et al. 2015

The Journal of Immunology

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CD4+CD25hi FOXP3+ regulatory T cells (Tregs) maintain tolerance to self-Ags. Their defective function is involved in the pathogenesis of multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS. However, the mechanisms of such defective function are poorly understood. Recently, we reported that stimulation of TLR2, which is preferentially expressed by human Tregs, reduces their suppressive function and skews them into a Th17-like phenotype. In this study, we tested the hypothesis that TLR2 activation is involved in reduced Treg function in MS. We found that Tregs from MS patients expressed higher levels of TLR2 compared with healthy controls, and stimulation with the synthetic lipopeptide Pam3Cys, an agonist of TLR1/2, reduced Treg function and induced Th17 skewing in MS patient samples more than in healthy controls. These data provide a novel mechanism underlying diminished Treg function in MS. Infections that activate TLR2 in vivo (specifically through TLR1/2 heterodimers) could shift the Treg/Th17 balance toward a proinflammatory state in MS, thereby promoting disease activity and progression.

show abstract

Section: Discussionmentioning

confidence: 99%

TLR2 Stimulation Regulates the Balance between Regulatory T Cell and Th17 Function: A Novel Mechanism of Reduced Regulatory T Cell Function in Multiple Sclerosis

Nyirenda

Morandi

Vinkemeier

et al. 2015

The Journal of Immunology

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“…Several studies identify IL-6 as an important player in the onset and exacerbation of MS, since its levels are increased in the serum and cerebrospinal fluid of MS patients (79)(80)(81), in MS lesions (82,83) and in mononuclear cells from cerebrospinal fluid and blood of MS patients (84). Auto-immune reactivity against minor components of myelin are thought to play an important role in the pathogenesis of multiple sclerosis.…”

Section: Il-6 and Multiple Sclerosismentioning

confidence: 99%

IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?

Camporeale

Poli²

2012

Front Biosci

158

107

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“…Elevated IL-6 levels have been observed in the CSF and plasma of multiple sclerosis (MS) patients (Frei et al 1991;Maimone et al 1991;Navikas et al 1996), and IL-6 immunoreactivity has been observed in acute and chronically active MS plaques (Maimone et al 1997). The concentration of sIL-6R is also increased in the CSF of MS patients compared with patients with other inflammatory neurological disorders (Michalopoulou et al 2004).…”

mentioning

confidence: 99%

Context‐dependent IL‐6 potentiation of interferon‐ gamma‐induced IL‐12 secretion and CD40 expression in murine microglia

Lin¹,

Levison²

2009

Journal of Neurochemistry

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Interleukin-6 (IL-6) is produced by neurons, astrocytes, and microglia, and elevated levels of IL-6 within the CNS have been documented in multiple neurological disorders including Alzheimer's disease, stroke, epilepsy, attention deficit disorder, cerebral palsy, and multiple sclerosis. Here, we sought to understand how IL-6 regulates microglial signal transduction and their immune properties. Using highly enriched cultures of neonatal murine microglia we show that IL-6 alone has direct effects on microglia as it activates STAT3 and extracellular signal-regulated kinase pathways in a time-and dosedependent fashion and it enhances interferon-gamma (IFNc)-stimulated IL-12 secretion. However, other immune properties were only weakly modulated by IL-6 when administered without the soluble IL-6 receptor (sIL-6R). For instance, IFNcinduced expression of the co-stimulatory molecule, CD40 was dependent on sIL-6R administration. IL-6 with or without sIL-6R did not affect major histocompatability complex class II expression. In granulocyte-macrophage colony-stimulating factor (GMCSF)-induced dendritic cell-like microglia, IL-6/sIL-6R and IFNc stimulated an even greater increase in CD40 expression compared with primary microglia. Altogether, our results demonstrate that microglial responses to IL-6 are not simple in that the effects of IL-6 are context-dependent. In particular, the presence or absence of sIL-6R, IFNc or GMCSF will alter the type and amplitude of their response.

show abstract

IL-6 detection in multiple sclerosis brain

Cited by 154 publications

References 32 publications

TLR2 Stimulation Regulates the Balance between Regulatory T Cell and Th17 Function: A Novel Mechanism of Reduced Regulatory T Cell Function in Multiple Sclerosis

TLR2 Stimulation Regulates the Balance between Regulatory T Cell and Th17 Function: A Novel Mechanism of Reduced Regulatory T Cell Function in Multiple Sclerosis

IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?

Context‐dependent IL‐6 potentiation of interferon‐ gamma‐induced IL‐12 secretion and CD40 expression in murine microglia

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