Cytokine signaling in multiple sclerosis: Lost in translation

Göbel, Kerstin; Ruck, Tobias; Meuth, Sven G.

doi:10.1177/1352458518763094

Cited by 92 publications

(74 citation statements)

References 58 publications

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“…Neuroinflammation is thought to play a role in many neuropsychiatric and neurological conditions [1][2][3][4]; however, its exact contribution remains poorly understood [5][6][7]. This is partially due to limited diagnostic tools to measure inflammation in the central nervous system (CNS) [8].…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

et al. 2019

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Purpose: The P2X7 receptor, an adenosine triphosphate (ATP)-gated purinoreceptor, has emerged as one of the key players in neuroinflammatory processes. Therefore, developing a positron emission tomography (PET) tracer for imaging of P2X7 receptors in vivo presents a promising approach to diagnose, monitor, and study neuroinflammation in a variety of brain disorders. To fulfill the goal of developing a P2X7 PET ligand as a biomarker of neuroinflammation, [ 18 F]JNJ-64413739 has been recently disclosed. Procedures: We evaluated [ 18 F]JNJ-64413739 in a rat model of neuroinflammation induced by an intracerebral injection of lipopolysaccharide (LPS). In vivo brain uptake was determined by PET imaging. Upregulation of neuroinflammatory biomarkers was determined by quantitative polymerase chain reaction (qPCR). Distribution of the tracer in the brain was determined by ex vivo autoradiography (ARG). The specificity of [ 18 F]JNJ-64413739 was confirmed by performing blocking experiments with the P2X7 antagonist JNJ-54175446. Results: Brain regions of rats injected with LPS had a significantly increased uptake (34 % ± 3 % s.e.m., p = 0.036, t test, standardized uptake value measured over the entire scanning period) of [ 18 F]JNJ-64413739 relative to the corresponding brain regions of control animals injected with phosphate-buffered saline (PBS). The uptake in the contralateral regions and cerebellum was not significantly different between the groups of animals. The increase in uptake of [ 18 F]JNJ-64413739 at the LPS-injected site observed by PET imaging was concordant with ex vivo ARG, upregulation of neuroinflammatory biomarkers, and elevated P2X7 expression levels. Conclusions: While further work is needed to study [ 18 F]JNJ-64413739 in other types of neuroinflammation, the current results favorably characterize [ 18 F]JNJ-64413739 as a potential PET tracer of central neuroinflammation.

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Section: Introductionmentioning

confidence: 99%

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

et al. 2019

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“…Indeed soluble mediators of inflammation released by activated lymphocytes and resident immune cells represent key regulators of the auto-immune response in MS. Specific proinflammatory molecules, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF), and interferon-gamma, promote immune cell infiltration through the blood-brain barrier, leading to demyelination and axonal damage (Göbel et al, 2018). In addition, experimental studies showed that proinflammatory molecules also alter neuronal functioning by promoting excitotoxic neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis

Bassi

Iezzi

Drulović

et al. 2020

Front. Cell. Neurosci.

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Specific proinflammatory and anti-inflammatory molecules could represent useful cerebrospinal fluid (CSF) biomarkers to predict the clinical course of multiple sclerosis (MS). The proinflammatory molecule interleukin (IL)-6 has been investigated in the pathophysiology of MS and has been associated in previous smaller studies to increased disability and disease activity. Here, we wanted to further address IL-6 as a possible CSF biomarker of MS by investigating its detectability in a large cohort of 534 MS patients and in 103 individuals with other non-inflammatory neurological diseases. In these newly diagnosed patients, we also explored correlations between IL-6 detectability, MS phenotypes, and disease characteristics. We found that IL-6 was more frequently detectable in the CSF of MS patients compared with their control counterparts as significant differences emerged between patients with Clinically isolated syndrome (CIS), Relapsing-remitting (RR), and secondary progressive and primary progressive MS compared to non-inflammatory controls. IL-6 was equally present in the CSF of all MS phenotypes. In RR MS patients, IL-6 detectability was found to signal clinically and/or radiologically defined disease activity, among all other clinical characteristics. Our results add further evidence that CSF proinflammatory cytokines could be useful for the identification of those MS patients who are prone to increased disease activity. In particular, IL-6 could represent an interesting prognostic biomarker of MS, as also demonstrated in other diseases where CSF IL-6 was found to identify patients with worse disease severity.

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“…These virulent factors hence trigger both the cellular and humoral immune responses [11,12,13]. Accordingly, cytokines responses have been found to play crucial role in the pathogenesis of most bacterial infection [14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

“…Cytokines as immunological mediators are involved in the immune build up in inflammatory conditions of the udder [18,19]. They are known for their cell signalling roles and anti-inflammatory pathways during infection as they strike a balance between the cellular and humoral immunity [20,21,17]. An experimental study following S. aureus intramammary challenge in lactating cows indicated that IL-12 is a good marker in response to S. aureus challenge and vaccination [22].…”

Section: Introductionmentioning

confidence: 99%

Acute Phase Proteins (Haptoglobin and Serum Amyloid A) and Pro-Inflammatory Cytokines (IL-12 and IL-10) in Cows Vaccinated with Prototype Killed S. aureus Mastitis Vaccine and Challenged with S. aureus Mastitis Infection.

Hambali

Abdallah

Bhuttu

et al. 2020

Preprint

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Background The economic downturn experienced by farmers and the fear of milk borne infection are of a greater public health concern. Haptoglobin, Serum Amyloid A, IL-12 and IL-10 in lactating Friesian cows vaccinated with prototype killed S. aureus mastitis vaccine and challenged with S. aureus were evaluated. Bacterin concentration at 10 8 cfu /ml of the local isolate of S. aureus was adjuvanted with KAl(SO₄)₂. Six lactating Friesian cows were grouped into A= Negative control, B = Positive control and C = vaccine group. Group C was vaccinated intramuscularly with 2ml of the monovalent vaccine, groups A and B with physiologic normal saline. Groups B and C were later challenged with the live bacterium via intramammary route . Result There was a significant increase in IL-10 concentration in vaccinated group post primary vaccination (PPV), booster phase (PB) and during the bacterial challenge phase. There was also a significantly increased IL-12 concentration in the vaccinated group at 24 hours, weeks 1 and 2 PPV. Haptoglobin at 12 and 24 hours PPV had a significant difference in group C. During the PB at 8 and 12 hours there was a significant difference in group C. During the bacterial challenged phase at 0, 3, 24 hours and day 7 PC there was a significant difference in group B. At 8 hours PC there was a significant difference in group C. For Serum Amyloid A, during PPV at 0, 3, 8, 12, 24 hours and weeks 1 and 2, the concentrations was significantly different in groups C. During PB at 0, 3, 8 and 12 hours PB there was a significant difference in groups C. During the bacterial challenge phase at 3, 8, 12, 24 hours, days 7 and 14 PC there was a significant difference in group B. At 0 hour PC there was a significant increase observed in group C. Conclusion The developed prototype killed S. aureus mastitis vaccine using local isolates was able to stimulate acute phase proteins and pro-inflammatory cytokines. The pattern of responses PC indicated protection, thereby suggesting that vaccination can protect against mastitis infection in dairy cows.

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Cytokine signaling in multiple sclerosis: Lost in translation

Cited by 92 publications

References 58 publications

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis

Acute Phase Proteins (Haptoglobin and Serum Amyloid A) and Pro-Inflammatory Cytokines (IL-12 and IL-10) in Cows Vaccinated with Prototype Killed S. aureus Mastitis Vaccine and Challenged with S. aureus Mastitis Infection.

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