Effect of the treatment with methylprednisolone on the cerebrospinal fluid and serum levels of CCL2 and CXCL10 chemokines in patients with active multiple sclerosis

Moreira, Marcos Aurélio; Tilbery, Charles Peter; Monteiro, L. P.; Teixeira, M.M.; Teixeira, Antônio Lúcio

doi:10.1111/j.1600-0404.2006.00629.x

Cited by 33 publications

(24 citation statements)

References 26 publications

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“…Another example demonstrating the complexity in interpreting MCP-1 results is that the neuroinflammatory condition multiple sclerosis has been associated with relatively low CSF levels of MCP-1, but high levels of another chemokine CXCL10. 33 In contrast to MCP-1, YKL-40 appears to be more expressed in microglia than in neurons or astrocytes. 34 Increased YKL-40 expression is characteristic of many chronic inflammatory conditions, such as rheumatoid arthritis and irritable bowel syndrome, that are associated with destruction of the extracellular matrix and tissue remodelling.…”

Section: Discussionmentioning

confidence: 99%

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Jakobsson

Bjerke

Sahebi

et al. 2015

jpn

100

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Section: Discussionmentioning

confidence: 99%

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Jakobsson

Bjerke

Sahebi

et al. 2015

jpn

100

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“…High-dose methylprednisolone treatment of MS patients leads to a reduction of CXCR-3 and CCR5 expression on peripheral blood T cells (Elovaara et al, 2006;Wang et al, 2003). In addition, a diminished level of CXCL10/IP-10, the ligand of CXCR3, and an elevated level of CCL2 were observed in the CSF of MS patients after GC therapy (Moreira et al, 2006). It is noteworthy that the role of CCL2 in MS is controversial, although it appears that it is linked to the polarization of T cells towards a TH2 phenotype (Moreira et al, 2006).…”

Section: Accepted Manuscript -11mentioning

confidence: 98%

“…In addition, a diminished level of CXCL10/IP-10, the ligand of CXCR3, and an elevated level of CCL2 were observed in the CSF of MS patients after GC therapy (Moreira et al, 2006). It is noteworthy that the role of CCL2 in MS is controversial, although it appears that it is linked to the polarization of T cells towards a TH2 phenotype (Moreira et al, 2006). Thus, influences on the expression of chemokine receptors and their ligands may also result from a T H 2 shift induced by GCs (see below).…”

Section: Accepted Manuscript -11mentioning

confidence: 99%

Glucocorticoids in the control of neuroinflammation

Tischner

Reichardt

2007

Molecular and Cellular Endocrinology

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Glucocorticoids are a class of steroid hormones that are endowed with profound antiinflammatory and immunosuppressive activities. Endogenous glucocorticoids are key players in the modulation of the immune system and establish an endocrine basis of many inflammatory diseases. In addition, synthetic glucocorticoids are amongst the most commonly prescribed drugs worldwide for the treatment of autoimmune disorders. In this review we summarize our present knowledge on the mechanisms by which glucocorticoids impact on multiple sclerosis (MS), a highly prevalent neuroinflammatory disease, and its animal model experimental autoimmune encephalomyelitis (EAE). In spite of the new methodologies that have become available during recent years, we are still far from a comprehensive picture of the mechanism by which glucocorticoids control neuroinflammation. Keywords: Glucocorticoids; Multiple Sclerosis; Experimental AutoimmuneEncephalomyelitis; Apoptosis; Blood-brain barrier Page 2 of 33A c c e p t e d M a n u s c r i p t -3 IntroductionGlucocorticoids (GCs) are a class of steroid hormones that are commonly used to treat acute and chronic inflammatory disorders (Tuckermann et al., 2005). They exert most of their functions by binding to the glucocorticoid receptor (GR), which controls gene expression and signalling cascades through genomic as we ll as non-genomic mechanisms. By this means, GCs modulate the survival, differentiation, migration and various effector functions of leukocytes and other cell types and thereby impact both, innate and adaptive immunity. W hilst GCs administered at pharmacological concentrations are considered purely immunosuppressive, fluctuations in the levels of endogenous GCs, e.g. during stress, result in more complex immunomodulatory effects (Elenkov and Chrousos, 1999).One major application of GCs is the treatment of neuroinflammatory disorders, in particular multiple sclerosis (MS), the most prevalent chronic autoimmune disease of the central nervous system (CNS) in the Western world (Noseworthy et al., 2000). MS is characterized by infiltrating autoreactive T-cells in the CNS that initiate aninflammatory cascade involving leukocytes and humoral components (Sospedra and Martin, 2005). This causes demyelination and axonal loss, which eventually leads to severe functional deficits. While GCs have no positive effect on the long-term prognosis of MS, optic neuritis and other acute relapses are widely treated with high doses of methylprednisolone (Milligan et al., 1987). Still, such a therapy may lead to severe complications or incomplete recovery. Furthermore, it is known that the course of MS is influenced by the level of endogenous GCs (Elenkov and Chrousos, 1999). Women in the third trimester of pregnancy and Cushing syndrome patients often experience remission of the disease. This is explained by a polarization of the immune system towards T H 2 dominated responses as a consequence of increased Page 3 of 33A c c e p t e d M a n u s c r i p t -4 cortisol synthesis. Thus, fluctuations in G...

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“…Cytokines were found to mediate hypernociception in a carrageenan-induced inflammatory model of hyperalgesia 10 and chemokines (chemotactic cytokines) seem to be involved in the hypernociception elicited by an experimental model of arthritis 24 . Chemokines are also important in MS 25,26 and they are involved in many pathways of pain 27 . The possibility of chemokines being the cause of pain in MS was discussed elsewhere 28 .…”

Section: Discussionmentioning

confidence: 99%

Mechanical hypernociception in experimental autoimmune encephalomyelitis

Rodrigues

Sachs

Teixeira

2009

Arq. Neuro-Psiquiatr.

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-Background:Pain is an important clinical manifestation in multiple sclerosis (MS) patients, though it has been neglected in clinical and experimental researches. Objective: To investigate the nociceptive response in MOG 35-55 experimental autoimmune encephalomyelitis (EAE)-induced mice. Method: EAE was induced in 8 to 10 week old C57BL/6 female mice with an emulsion of MOG , Complete Freund Adjuvant, Mycobacterium tuberculosis H37 RA and pertussis toxin. Nociception was evaluated by the von Frey filaments method. A clinical scale ranging from 0 to 15 was used to assess motor impairment. Results: Clinical evidence of disease started at day 10 and peaked at day 14 after immunization. Thereafter, there was no worsening of symptoms until day 26. The EAE-induced mice presented reduced pressure threshold at days 7 th and 10 th after immunization and before the onset of clinical motor signs. Conclusion: The hypernociception found validates MOG 35-55 EAE as a model for the study of pain in multiple sclerosis.KEY WORDS: multiple sclerosis; experimental autoimmune encephalomyelitis, hyperalgesia, mechanical hypernociception. hipernocicepção mecânica em encefalomielite autoimune experimentalResumo -Introdução: Dor é uma manifestação importante em pacientes com esclerose múltipla (EM), mas que tem sido negligenciada na pesquisas clínica e experimental. Objetivo: Investigar a resposta nociceptiva de camundongos com encefalomielite autoimune experimental (EAE) induzida por MOG . Método: A EAE foi induzida em camundongos C57BL/6 fêmeas de 8-10 semanas com emulsão contendo MOG 35-55 , Adjuvante Completo de Freund, Mycobacterium tuberculosis cepa H37 RA e toxina pertussis. A nocicepção foi medida pelo método de filamentos de von Frey. Uma escala clínica variando de 0 a 15 foi utilizada para avaliar a debilidade motora dos animais. Resultados: Os sinais clínicos da doença iniciaram-se no dia 10 e a gravidade máxima foi alcançada no dia 14 após a imunização. Não houve piora dos sintomas até o dia 26. Os camundongos induzidos com EAE apresentaram diminuição do limiar de pressão nos dias 7 e 10 após a imunização e antes do início dos sinais motores. Conclusão: A hipernocicepção verificada valida a EAE induzida por MOG 35-55 como um modelo para estudos de dor em esclerose múltipla. PALAVRAS-CHAVE: esclerose múltipla; encefalomielite autoimune experimental, hiperalgesia; hipernocicepção mecânica.

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Effect of the treatment with methylprednisolone on the cerebrospinal fluid and serum levels of CCL2 and CXCL10 chemokines in patients with active multiple sclerosis

Abstract: The clinical improvement of active MS following the treatment with methylprednisolone was associated with the modification of CSF levels of CCL2 and CXCL10, suggesting that these chemokines may be useful markers of response to treatment and relapses in MS patients.

Cited by 33 publications

References 26 publications

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Glucocorticoids in the control of neuroinflammation

Mechanical hypernociception in experimental autoimmune encephalomyelitis

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