Evaluation of Serum Levels of Chemokines during Interferon-β Treatment in Multiple Sclerosis Patients

Comini-Frota, Elizabeth Regina; Teixeira, Antônio Lúcio; Angelo, Janaína P. A.; Andrade, Marcus V.; Brum, Doralina Guimarães; Kaimen-Maciel, Damacio Ramón; Foss, Norma T.; Donadi, Eduardo Antônio

doi:10.2165/11595060-000000000-00000

Cited by 17 publications

(15 citation statements)

References 46 publications

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“…Specifically, CXCL10 was higher in acute MS and lower in stable disease, suggesting a pathogenetic role for the chemokine in mediating clinical re-exacerbation of MS (45). In addition, the previously reported inverse correlation between CXCL10 levels and time from last clinical relapse, together with the finding that CXCL9, CXCL10, and CXCL11 are up-regulated during relapse in MS (46)(47)(48), strongly supports this hypothesis.…”

Section: Discussionsupporting

confidence: 59%

Increase of Interferon-γ Inducible CXCL9 and CXCL11 Serum Levels in Patients with Active Graves' Disease and Modulation by Methimazole Therapy

Antonelli

Ferrari

Corrado

et al. 2013

Thyroid

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Section: Discussionsupporting

confidence: 59%

Increase of Interferon-γ Inducible CXCL9 and CXCL11 Serum Levels in Patients with Active Graves' Disease and Modulation by Methimazole Therapy

Antonelli

Ferrari

Corrado

et al. 2013

Thyroid

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“…RANTES was previously described as different between men and women in a study where PDGF-BB and RANTES were measured to describe gender differences in chemokine as marker of atherosclerosis [19]. Another study showed different fluctuations of MIP-1βconcentration in women, but not men affected with multiple sclerosis, [20], suggesting a relationship between gender and plasma levels of MIP-1β. This could also be due to the predominance of women in our cohort (65%).…”

Section: Discussionmentioning

confidence: 99%

Baseline Levels and Temporal Stability of 27 Multiplexed Serum Cytokine Concentrations in Healthy Subjects

et al. 2013

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BackgroundCytokines are humoral molecules that elicit regulatory function in immunologic pathways. The level and type of cytokine production has become critical in distinguishing physiologic from pathologic immune conditions. Cytokine profiling has become an important biomarker discovery tool in monitoring of the immune system. However, the variations in cytokine levels in individual subjects over time in healthy individuals have not been extensively studied. In this study, we use multiplex bead arrays to evaluate 27 analytes in paired serum samples taken seven days apart from 144 healthy individuals in order to assess variations over a short time period.MethodsFluorescent bead-based immunoassay (Luminex) was used to measure 27 analytes in serum samples. Measurements were performed on matched samples from 144 healthy donors. To assess inter-plate variability, one arbitrarily selected serum sample was analyzed on each of the first ten plates as bridge sample. ResultsUsing the bridge sample, we showed minimal inter-plate variations in the measurement of most analytes. In measurement of cytokines from the 144 patients at two time points, we found that three cytokines (IL-2, IL-15 and GM-CSF) were undetectable and five analytes (RANTES, MCP-1, VEGF, MIP-1β and PDGF-BB) showed significant difference in concentrations at Day 0 compared to Day 7. ConclusionsThe current study demonstrated higher variations in cytokine levels among individuals than were observed for samples obtained one week apart from identical donors. These data suggest that a serum sample from each subject for use as a baseline measurement is a better control for clinical trials rather than sera from a paired cohort.

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“…Regression analysis indicated a significant linear relationship between CSF cell count and CXCL10 concentrations in the CSF (97). CominiFrota et al (99) reported that serum levels of CXCL10 are elevated in MS patients and correlated positively with relapses and IFN-b-1a/b-immunomodulatory therapy. Histopathological studies revealed that CXCL10 immunoreactivity is mainly associated with astrocytes around inflammatory lesions (97, 100-102), as described previously in EAE (103)(104)(105).…”

Section: Significance Of the Study Using The Cuprizone Modelmentioning

confidence: 96%

CXCL10 Triggers Early Microglial Activation in the Cuprizone Model

Clarner

Janssen

Nellessen

et al. 2015

The Journal of Immunology

118

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A broad spectrum of diseases is characterized by myelin abnormalities and/or oligodendrocyte pathology. In most, if not all, of these diseases, early activation of microglia occurs. Our knowledge regarding the factors triggering early microglia activation is, however, incomplete. In this study, we used the cuprizone model to investigate the temporal and causal relationship of oligodendrocyte apoptosis and early microglia activation. Genome-wide gene expression studies revealed the induction of distinct chemokines, among them Cxcl10, Ccl2, and Ccl3 in cuprizone-mediated oligodendrocyte apoptosis. Early microglia activation was unchanged in CCL2- and CCL3-deficient knockouts, but was significantly reduced in CXCL10-deficient mice, resulting in an amelioration of cuprizone toxicity at later time points. Subsequent in vitro experiments revealed that recombinant CXCL10 induced migration and a proinflammatory phenotype in cultured microglia, without affecting their phagocytic activity or proliferation. In situ hybridization analyses suggest that Cxcl10 mRNA is mainly expressed by astrocytes, but also oligodendrocytes, in short-term cuprizone-exposed mice. Our results show that CXCL10 actively participates in the initiation of microglial activation. These findings have implications for the role of CXCL10 as an important mediator during the initiation of neuroinflammatory processes associated with oligodendrocyte pathology.

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Evaluation of Serum Levels of Chemokines during Interferon-β Treatment in Multiple Sclerosis Patients

Abstract: ISRCTN45526724.

Cited by 17 publications

References 46 publications

Increase of Interferon-γ Inducible CXCL9 and CXCL11 Serum Levels in Patients with Active Graves' Disease and Modulation by Methimazole Therapy

Increase of Interferon-γ Inducible CXCL9 and CXCL11 Serum Levels in Patients with Active Graves' Disease and Modulation by Methimazole Therapy

Baseline Levels and Temporal Stability of 27 Multiplexed Serum Cytokine Concentrations in Healthy Subjects

CXCL10 Triggers Early Microglial Activation in the Cuprizone Model

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