Efeito do soro e do aquecimento de linfócitos sobre a resposta blastogenica

BV UNIFESP: Teses e dissertaçõe

Disruption of melatonin circadian rhythm production is related to multiple sclerosis severity: a preliminary study

Sunlight can influence the immune system independently of vitamin D, such as through melatonin production in the pineal gland. Inflammatory disorders can suppress nocturnal melatonin production, but only a few studies have investigated melatonin status in multiple sclerosis (MS). We aimed to study melatonin production in association with clinical and immunological data in MS patients. Eleven treated relapsing-remitting MS (RRMS) patients and eight controls underwent neurological examination and were assessed for fatigue severity and depressive symptoms. Inflammatory cytokines were analyzed in blood samples and concentration of 6-sulfatoxymelatonin (6-SMT) was determined in 24h urine. Patients with an abnormal proportion of overnight 6-SMT (n=8, 72.7%) had higher disability and fatigue severity (p<0.05). Overnight 6-SMT was inversely related with fatigue severity (p=0.016), number of relapses in the previous 12 months (p=0.010) and EDSS scores (p=0.049). In conclusion, disruption of melatonin circadian rhythm production is frequent among RRMS patients and seemingly related to higher disability and fatigue scores. Future studies with larger sample size are necessary to establish melatonin status as a biomarker of disease severity in MS.Sunlight can influence the immune system independently of vitamin D, such as through melatonin production in the pineal gland. Inflammatory disorders can suppress nocturnal melatonin production, but only a few studies have investigated melatonin status in3531166168FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2010/00885-4This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (PhD grant number 2010/00885-4). Alfredo Damasceno would like to thank Professor Regina P. Markus, from the Department of Physiology, University of São Paulo, for he

Serum Bdnf Levels Are Not Reliable Correlates Of Neurodegeneration In Ms Patients.

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A spring to summer shift of pro-inflammatory cytokine production in multiple sclerosis patients

Higher MS relapse frequency is observed during warmer months in different regions, but evidence for an underlying immunological variation is lacking. Therefore, we investigated seasonal variations of cytokine production in relapsing-remitting MS patients. Twenty-one patients and eight controls had blood samples drawn in each season, evaluating for IL-10, IL-6, TNF-α and IFN-γ. The lowest levels of cytokine production were observed in spring samples, with a significant increase from spring to summer for most cytokines, and especially IFN-γ and TNF-α. This phenomenon may underlie the higher prevalence of clinical and subclinical MS activity observed in warmer months.Higher MS relapse frequency is observed during warmer months in different regions, but evidence for an underlying immunological variation is lacking. Therefore, we investigated seasonal variations of cytokine production in relapsing-remitting MS patients.3603740FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR2010/00885-4SEM INFORMAÇÃOThis work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (PhD grant number 2010/00885-4) andCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).The authors would like to thank all patients and volunteers wh

Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg) cells and suppressive Dendritic Cells (DCs), to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ), an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE), an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS) and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of EAE-inflicted mice, both in prophylactic and therapeutic approaches. We hypothesized that the increased number of regulatory T cells induced by the CQ treatment is involved in the reduction of the clinical signs of EAE

Cytokines and intrathecal IgG synthesis in multiple sclerosis patients during clinical remission Citocinas e síntese intratecal de IgG em pacientes com esclerose múltipla durante remissão clínica

Cytokines and intrathecal IgG synthesis were determined in the cerebrospinal fluid (CSF) and sera to evaluate inflammatory activity in multiple sclerosis (MS) patients during clinical remission. Although the disease was stable, there had been a significant increase of proinflammatory cytokines such as TNFalpha and IFNgamma in the CSF and serum, with no significant changes of IL12 and IL10 production. The changes in the cytokine production patterns were associated with an increase of leukocytes in the CSF, as well as the presence of oligoclonal bands suggesting intrathecal IgG synthesis. These results suggest that even when the disease is clinically silent, one can observe inflammatory activity in these MS patients.Os níveis de citocinas e síntese intratecal de IgG foram dosados no líquido cefalorraquidiano (LCR) e soro, com o objetivo de avaliar a atividade inflamatória em pacientes com esclerose múltipla durante remissão clínica. Foram detectados níveis elevados de citocinas pró-inflamatórias (TNFalfa e IFNgama) no LCR e soro, sem alterações significativas na produção de IL12 e IL10. O perfil de produção das citocinas pró-inflamatórias estava associado ao aumento de leucócitos no LCR, assim como a presença de bandas oligoclonais IgG sugerindo síntese intratecal de IgG. Estes resultados sugerem que mesmo quando a doença está clinicamente silenciosa, a atividade inflamatória está presente nestes pacientes

Chloroquine administration alters the frequency of regulatory T (Treg) cells and dendritic cells (DCs), but not the proliferative capability of T cells.

<p>Briefly, mice were treated with chloroquine via i.p. for five consecutive days. Three days after the last dose mice were killed and splenic cells were analyzed by flow cytometry. Increased numbers of Treg cells (A) and reduced frequency of DCs (B) was found in mice treated with chloroquine when compared to the control group. In addition, splenic T cells proliferative response was not altered in the presence of concanavalin-A (C). Subpopulations of leukocytes showed slight changes when compared to control subjects (D). Results are representative of three independent experiments.</p

Analysis of the cellular infiltration of the CNS show reduced IFN-γ and IL-17 producing cells in CQ treated EAE mice.

<p>(A) CQ treated-mice presented reduced infiltration of inflammatory cells. (B) The percentage of IFN-γ- and IL-17-producing cells infiltrating the brain was reduced while the frequency of IL-10- producing cells was found augmented in brain of mice treated with CQ. (C, D and E) Gene expression of IFN-γ, IL-17 and IL-10 in the CNS followed the same pattern, respectively. (F) The expression of FOXP3 was evaluated in the CNS by RT-PCR. (G) The frequency of CD25⁺Foxp3⁺ cells was evaluated in spleens of mice. Results are representative of two independent experiments and are expressed as mean ± SEM for at least five animals. p<0,05 (*) and p<0.01 (**).</p