Development of a translational inflammation panel for the quantification of cerebrospinal fluid Pterin, Tryptophan-Kynurenine and Nitric oxide pathway metabolites

Yan, Jingya; Han, Velda X.; Heng, Benjamin; Guillemin, Gilles J.; Bandodkar, Sushil; Dale, Russell C.

doi:10.1016/j.ebiom.2022.103917

Cited by 13 publications

(12 citation statements)

References 44 publications

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“…The ratio between anthranilic acid and 3HAA correlates with inflammatory status in many disorders ( Forrest et al, 2006 ; Darlington et al, 2010 ; Heng et al, 2020 ; Huang et al, 2020 ; Jusof et al, 2022 ; Yan et al, 2022 ) and 3HAA contributes to allograft survival ( He et al, 2015 ), synergistically with AHR activation ( Gargaro et al, 2019 ). Kynurenine, kynurenic acid and 3HAA reduce NK cell activation and proliferation, potentially facilitating tumor development ( Fallarino et al, 2002 ; Terness et al, 2002 ; Hayashi et al, 2007 ).…”

Section: An Integrated Kynurenine-cytokine Systemmentioning

confidence: 99%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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Two of the molecular families closely associated with mediating communication between the brain and immune system are cytokines and the kynurenine metabolites of tryptophan. Both groups regulate neuron and glial activity in the central nervous system (CNS) and leukocyte function in the immune system, although neither group alone completely explains neuroimmune function, disease occurrence or severity. This essay suggests that the two families perform complementary functions generating an integrated network. The kynurenine pathway determines overall neuronal excitability and plasticity by modulating glutamate receptors and GPR35 activity across the CNS, and regulates general features of immune cell status, surveillance and tolerance which often involves the Aryl Hydrocarbon Receptor (AHR). Equally, cytokines and chemokines define and regulate specific populations of neurons, glia or immune system leukocytes, generating more specific responses within restricted CNS regions or leukocyte populations. In addition, as there is a much larger variety of these compounds, their homing properties enable the superimposition of dynamic variations of cell activity upon local, spatially limited, cell populations. This would in principle allow the targeting of potential treatments to restricted regions of the CNS. The proposed synergistic interface of ‘tonic’ kynurenine pathway affecting baseline activity and the superimposed ‘phasic’ cytokine system would constitute an integrated network explaining some features of neuroimmune communication. The concept would broaden the scope for the development of new treatments for disorders involving both the CNS and immune systems, with safer and more effective agents targeted to specific CNS regions.

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Section: An Integrated Kynurenine-cytokine Systemmentioning

confidence: 99%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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“…Contrary to what was thought for decades, ocular fluids are not independent of CSF; communication can occur through the optic nerve and the perivascular space of the central retinal artery [ 21 , 22 , 23 ]. Hence, the study of the composition of AH may lead to finding some biomarkers of neuroinflammation of those recently reported for some neurological diseases [ 24 ]. Consistent with the hypothesis of a neuroinflammatory component in diabetes, there was an increase in the level of kynurenine, which is related to microglial activation/neuroinflammation [ 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Biogenic Amine Levels Markedly Increase in the Aqueous Humor of Individuals with Controlled Type 2 Diabetes

Lillo

Marín

Serrano-Marín

et al. 2022

IJMS

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The composition of the aqueous humor of patients with type 2 diabetes is relevant to understanding the underlying causes of eye-related comorbidities. Information on the composition of aqueous humor in healthy subjects is limited due to the lack of adequate controls. To carry out a metabolomics study, 31 samples of aqueous humor from healthy subjects without ocular pathology, submitted to refractive surgery and seven samples from patients with type 2 diabetes without signs of ocular pathology related to diabetes were used. The level of 25 compounds was significantly (p < 0.001) altered in the aqueous humor of the patient group. The concentration of a single compound, N-acetylornithine, makes it possible to discriminate between control and diabetes (sensitivity and specificity equal to 1). In addition, receptor operating characteristic curve and principal component analysis for the above-mentioned six compounds yielded significantly (p < 0.001) altered in the aqueous humor of the patient group. In addition, receptor operating characteristic curve and principal component analysis for six compounds yielded cut-off values and remarkable sensitivity, specificity, and segregation ability. The altered level of N-acetylornithine may be due to an increased amount of acetate in diabetes. It is of interest to further investigate whether this alteration is related to the pathogenesis of the disease. The increase in the amino form of pyruvate, alanine, in diabetes is also relevant because it could be a means of reducing the formation of lactate from pyruvate.

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“…The CSF tube analysed for this study was not used for routine testing and thawed only once after sampling. The tryptophan-kynurenine pathway metabolites (TRP, KYN, KYNA, 3-HK, XAN, AA, 3-HAA, QUIN, and picolinic acid) were measured according to the method of Yan et al 38 Briefly, 80 μL of human CSF was deproteinised with 20 μL of metaphosphoric acid/ethylenediaminetetraacetic acid solution, vortexed and centrifuged in Nanosep 0.2 μM centrifugal devices. The collected supernatant was analysed using a Waters ACQUITY UPLC I-Class System UPLC system coupled to a Xevo TQ-XS triple quadrupole mass spectrometer.…”

Section: Methodsmentioning

confidence: 99%

Decreased cerebrospinal fluid kynurenic acid in epileptic spasms: A biomarker of response to corticosteroids

et al. 2022

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Development of a translational inflammation panel for the quantification of cerebrospinal fluid Pterin, Tryptophan-Kynurenine and Nitric oxide pathway metabolites

Cited by 13 publications

References 44 publications

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

Biogenic Amine Levels Markedly Increase in the Aqueous Humor of Individuals with Controlled Type 2 Diabetes

Decreased cerebrospinal fluid kynurenic acid in epileptic spasms: A biomarker of response to corticosteroids

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