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ABSTRACT: The pathological hallmarks of multiple sclerosis (MS) lesions are inflammation, demyelination, axon loss and gliosis. The aim of this study was to verify the relation of brain lesion load and volume of the cerebral hemisphere determined by brain MRI with intrathecal antibody synthesis.
A longitudinal study of 54 Brazilian patients with the relapsing-remitting form of MS was undertaken after an average of 6.3 ± 2.7 years of treatment. MRI scans were performed, and cerebrospinal fluid samples were collected both during the diagnostic process and after treatment with β-interferon or glatiramer acetate.
A positive correlation between the IgG index and total lesion volume was identified. Intrathecal IgG against Epstein-Barr virus (EBV) was observed in 21 patients. The number of contrast-enhanced lesions observed in these patients was correlated with intrathecal IgM synthesis. Brain atrophy was observed early in the disease, with the number of relapses inversely correlated with brain volume.
The high intrathecal IgG synthesis observed in these relapsing-remitting MS patients is associated with the brain lesion burden and the presence of antibodies to EBV, whereas intrathecal IgM synthesis is associated with the activity of the disease, as revealed by MRI.
NeuroImmunoModulation 03/2012; 19(5):277-82. · 2.38 Impact Factor
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ABSTRACT: Immunotherapy with Interferon-beta (IFNbeta) results in remarkably beneficial effects in patients with relapsing-remitting multiple sclerosis (MS), although the mechanisms by which it exerts these beneficial effects remain poorly understood. An investigation was made of the effects of IFNbeta on pro-inflammatory and anti-inflammatory cytokine production in peripheral blood cells in MS patients, both untreated and those undergoing immunotherapy, as well as in healthy controls. Results show a significant increase in the production of pro-inflammatory cytokines such as TNFalpha, IFNgamma and IL-12 in the plasma and in the supernatant of leukocyte cultures from MS patients with the untreated disease; IFNbeta administration significantly reduced the levels of TNFalpha and IFNgamma, with no changes in the level of IL-12. The Interferon-beta therapy also led to a significant increase in the production of IL-10, as well as a slight increase in that of TGFbeta. The reduction in pro-inflammatory cytokine production in the treated MS patient group, accompanied by a simultaneous increase in the production of anti-inflammatory cytokines and the reduction of relapse rates suggests that the beneficial effects of IFNbeta immunotherapy result, at least in part, from the modulation of cytokine patterns.
International immunopharmacology 04/2009; 9(7-8):824-30. · 2.21 Impact Factor
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ABSTRACT: It was the aim of this study to evaluate if the quantitative intrathecal immunoglobulin G (IgG) synthesis correlates with the brain atrophy and the total lesion volume (TLV) in brain magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients.
A total of 50 patients with relapsing-remitting MS were included in this study. MRIs were performed and cerebrospinal fluid samples were collected during the diagnostic determination when patients were in remission without treatment.
At study baseline, IgG index values were elevated in 36 patients (72%), and oligoclonal IgG bands were positive in 42 of 50 patients (84%). Brain MRI was abnormal in 94% of patients, and, compared with healthy controls, brain atrophy was observed in MS patients. A positive correlation among IgG index, cerebrospinal fluid leukocyte count and TLV was observed; the Expanded Disability Status Scale correlated positively with TLV and the number of lesions, although a significant relationship between disability and brain atrophy was not demonstrated.
Although new parameters will be necessary in longitudinal studies to characterize the axonal injury in various stages of the disease, the data suggest that the high intrathecal IgG synthesis may predict a greater brain lesion burden.
NeuroImmunoModulation 02/2006; 13(2):89-95. · 2.38 Impact Factor
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ABSTRACT: Adjuvant-induced arthritis (AA) is thought to be a model for experimental chronic stress that has as main features decreased adrenocorticotropin hormone (ACTH) plasma levels and a rise in median eminence content of arginine vasopressin (AVP) due to the activity of substance P. In experimental allergic encephalomyelitis (EAE), another chronic stress model, the role of substance P action is not clear. In this paper we tried to clarify the role of substance P in Lewis rats, which are susceptible to this disease. EAE was induced using myelin basic protein plus complete Freund's adjuvant injected into the hind limbs. One day later injections of an antagonist to substance P (RP 67580), saline, and substance P were administered daily for 12-14 days through a stainless steel cannula into the lateral ventricle of the brain, and then the rats were killed. The rats were divided into groups of controls, sham, diseased controls (no intracerebroventricular injections) and EAE (injected intracerebroventricularly). Plasma was used for the quantification of ACTH and corticosterone but not AVP which was assayed in hypothalamic median eminence extracts. In noninjected diseased rats the plasma levels of ACTH and corticosterone were significantly higher than in noninjected control rats, whereas the AVP concentrations in the median eminence were unchanged. The substance P antagonist did not affect the levels of these hormones in plasma or the median eminence. Substance P decreased the plasma levels of ACTH and corticosterone but did not increase the median eminence content of vasopressin. Administration of the antagonist 30 min before an equivalent dose of substance P increased the plasma levels of the two hormones, but did not change the content of AVP. Based on the lack of response to the antagonist RP 67580 we suggest that the substance P has different roles in EAE and AA at least in the later stages of EAE (after 11 days of immunization).
NeuroImmunoModulation 02/2004; 11(1):28-35. · 2.38 Impact Factor
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ABSTRACT: Immunotherapy with Interferon-beta (IFNβ) results in remarkably beneficial effects in patients with relapsing-remitting multiple sclerosis (MS), although the mechanisms by which it exerts these beneficial effects remain poorly understood. An investigation was made of the effects of IFNβ on pro-inflammatory and anti-inflammatory cytokine production in peripheral blood cells in MS patients, both untreated and those undergoing immunotherapy, as well as in healthy controls.Results show a significant increase in the production of pro-inflammatory cytokines such as TNFα, IFNγ and IL-12 in the plasma and in the supernatant of leukocyte cultures from MS patients with the untreated disease; IFNβ administration significantly reduced the levels of TNFα and IFNγ, with no changes in the level of IL-12. The Interferon-beta therapy also led to a significant increase in the production of IL-10, as well as a slight increase in that of TGFβ.The reduction in pro-inflammatory cytokine production in the treated MS patient group, accompanied by a simultaneous increase in the production of anti-inflammatory cytokines and the reduction of relapse rates suggests that the beneficial effects of IFNβ immunotherapy result, at least in part, from the modulation of cytokine patterns.
International Immunopharmacology.
