Dysregulation of IL-10 and IL-12p40 in secondary progressive multiple sclerosis

Multiple sclerosis (MS) is a putative T helper 1 (Th-1) mediated inflammatory disorder of the central nervous system, and levels of pro-inflammatory and anti-inflammatory cytokines have been found to correlate with changes in MS relapses. However, it is unclear if cytokine profiles differ between relapsing-remitting (RRMS) versus secondary progressive (SPMS) disease stages. Cytokine production (IL-2, IL-4, IL-5, IL-10, IL-12p40, TNF-alpha, and IFN-gamma) was assessed by cytometric bead array (CBA) and intracellular cytokine staining from alphaCD3 antibody and mitogen stimulated peripheral blood mononuclear cells (PBMCs) from female RRMS and SPMS patients, and healthy controls. Significantly increased production of IL-12p40 and decreased production of IL-10 were observed in SPMS patients. Differences in immune responsiveness in RRMS and SPMS are important in the understanding of the evolution of the immunopathogenesis of the disease and for the development of disease type specific treatments.     

Augmented type 1 cytokines and human endogenous retroviruses specific immune responses in patients with acute multiple sclerosis

In vitro antigen- and mitogen-stimulated cytokine production were analysed in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). We also investigated whether immune responses to human endogenous retroviruses (HERV) could be detected in MS and whether these immune responses would be correlated with disease status by analysing cytokine production after stimulation of PBMC with HERV peptides. Results showed that mitogen-stimulated IL-2 and IFN-gamma was augmented and IL-10 was decreased in AMS compared to both SMS and healthy controls. Whereas the production of the metabolically active IL-12 (p70 heterodimer), was comparable in SMS, AMS and HC, production of the total IL-12 (p70 heterodimer and the p40 chain) were augmented in SMS compared to both AMS and HC. HERV-peptides IL-2 and IFN-gamma production was more frequent and more potent in AMS compared to both SMS patients and HC. HERV-specific type 2 cytokine production was more frequent and potent in SMS compared to AMS and HC. Thus a prevalent type 1 cytokine profile was seen in AMS patients, while IL-10 production predominated in SMS individuals.     

Cytokine secretion profile of myelin basic protein-specific T cells in multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a presumed autoimmune pathogenesis involving autoantigen-specific CD4+ T cells and cytokines. A similar frequency of T cells responding to myelin basic protein (MBP), a putative target in MS, has been observed in MS patients and controls. To dissect the differences between MBP-specific T cells in patients and controls, we have analyzed the cytokine secretion profile of such autoreactive T cells. MBP-specific T cell clones (TCC) were isolated from the peripheral blood of MS patients and controls by limiting dilution. Expression of mRNA for interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) was assessed by polymerase chain reaction whereas secretion of cytokine protein was measured by ELISA. MBP-specific TCC exhibited a heterogeneous cytokine secretion profile with clones displaying Th1, Th2 and Th0 phenotypes. A significant difference in the distribution of the cytokine profile was noted between MS patients and controls. Although the frequency of Th1 secreting MBP-reactive TCC was similar between MS patients and controls, stable MS patients had a significant association with the Th0 phenotype whereas healthy individuals were associated with the Th2 phenotype. In comparison to control TCC, MBP-specific TCC from MS patients secreted increased amounts of IFN-gamma, IL-4 and IL-10 and decreased quantities of TGF-beta. Thus, these studies suggest that there is a dysregulation in the balance between pro-inflammatory Th1 and anti-inflammatory Th2 cytokines in MS. It appears that the presence of Th1 secreting autoreactive T cells in healthy individuals may be counterbalanced by the presence of cells secreting Th2 cytokines and by the augmented production of the immunosuppressive cytokine TGF-beta, whereas in MS there is a decrease in these anti-inflammatory agents.     

The immunomodulatory properties of in vitro immunoglobulins are dose-dependent

OBJECTIVES: The mechanism by which intravenous immunoglobulins (immunoglobulin G, IgG) exert their beneficial effect on multiple sclerosis (MS) is unknown. Furthermore, there is uncertainty about the optimal dosage of IgG. Therefore, we investigated the influence of different IgG dosages on cytokine production in MS. MATERIALS AND METHODS: Twenty-five MS patients and 15 healthy controls were enrolled. We measured the production of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF) and interleukin 10 (IL-10) in peripheral blood lymphocytes by flowcytometry after stimulation without and with IgG in different doses (1, 5 and 10 mg/ml). RESULTS: IFN-gamma and TNF were decreased significantly (P = 0.001) in the untreated and interferon beta (IFN-beta) treated patients after stimulation with IgG. In contrast, IL-10 production was significantly enhanced (P = 0.001) at least in the untreated patient group. The reduction of the pro-inflammatory cytokines IFN-gamma and TNF after stimulation with different IgG doses was clearly dose-dependent in all groups. CONCLUSION: Besides a suppression of the pro-inflammatory cytokines IFN-gamma and TNF, IgG enhances the anti-inflammatory cytokine IL-10. This effect is dose-dependent, speaking in favour of higher IgG doses in the treatment of MS.     

Interferon-beta regulates cytokines and BDNF: greater effect in relapsing than in progressive multiple sclerosis

The mechanism of action of interferon (IFN)-beta therapy in multiple sclerosis (MS) is only partially known, and its efficacy changes with disease stage. In different forms of MS, we determined how IFN-beta regulates mononuclear cell production of the important anti-inflammatory Th2 cytokine - IL-10, the Th1 cytokine - IFN-gamma, and the brain-derived neurotrophic protein - BDNF. Activated T cells and monocytes from therapy-na?ve patients secreted more IL-10 than healthy controls. During IFN-beta therapy, however, T cells produced less IL-10. In vitro, IFN-beta stimulated IL-10 production by activated T cells, but inhibited IL-10 secretion by activated monocytes, a richer source of IL-10 than T cells. The form of MS also affected cytokine production. IL-10 and BDNF levels in MNC were high during relapsing/remitting (RR) MS, but low in progressive MS. Surprisingly, IFN-beta therapy increased BDNF levels in antidepressant-na?ve patients, but BDNF was lower during concurrent antidepressant drug therapy, suggesting an interaction between MS, depression, and neurodegeneration. IFN-beta in vitro strongly induced IL-10 and IFN-gamma in activated T cells in RRMS, but not in progressive MS, suggesting IFN resistance. IFN-beta effects are specific for disease state and immune subsets, possibly explaining why IFN-beta therapy is most effective in early T cell-regulated RRMS, but less beneficial in progressive MS, where chronic plaques contain few T cells and high numbers of monocytes.     

Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis

Sympathoadrenergic mechanisms may play a role in multiple sclerosis (MS). We examined catecholamine (CA) levels and production and tyrosine hydroxylase (TH) expression in peripheral blood mononuclear cells (PBMCs) from MS patients, and the correlation between CA production and apoptosis in PBMCs. PBMCs from MS patients had increased norepinephrine (NE) levels. However, phytohaemagglutinin (PHA)-stimulated PBMCs from MS patients with active disease synthesized less dopamine (DA) than cells from both healthy controls and patients with inactive disease. PBMCs from patients with inactive disease showed lower expression of TH. Pharmacological inhibition of TH in cultured PBMCs stimulated with PHA reduced the percentage of apoptotic cells. Since a failure of activation-induced apoptosis in immune cells may be involved in MS, it is suggested that altered CA production by PBMCs may be implicated in such dysregulation.     

Production of brain-derived neurotrophic factor by mononuclear cells of patients with multiple sclerosis treated with glatiramer acetate, interferon-beta 1a, and high doses of immunoglobulins

Sixty, relapsing remitting (RR) multiple sclerosis (MS) patients, who underwent treatment with glatiramer acetate (GA), interferon (IFN)-beta 1a, and immunoglobulins (Igs) (20 per treatment group), were assessed for levels of brain-derived neurotrophic factor (BDNF) in the supernatants of unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) in the first year of treatment. Phytohemagglutinin (PHA), anti-OKT3 antibody, myelin basic protein (MPB) and GA were used as stimuli. Cytokine responses by ELISPOT and lymphoproliferative responses were also assessed. The GA-treated MS patient group showed a progressive increase in BDNF levels, from baseline to month three; thereafter, the levels remained stable and significantly greater compared with baseline and controls (ANOVA=P<0.001). IFN-beta 1a had no effect on BDNF production, whereas Igs induced a slight decrease (ANOVA=P<0.04). ELISPOT analysis revealed a significant decrease of IFN-gamma, an increase of interleukin (IL)-4 and IL-5 in GA-treated MS patients, and an increase of IL-10 in patients treated with IFN-beta 1a and GA. No significant correlation was found between BDNF secretion in the supernatants of PBMCs and cytokine response, lesional load, and measures of atrophy. Increased BDNF production related to GA treatment can have implications for understanding the mechanism of action of this immunomodulatory agent, in light of evidence suggesting its effects in promoting neuroprotective immunity in MS patients; however, a clinically measurable effect, especially in terms of an impact on actual disease progression, remains to be established.     

Interleukin-12 is detectable in sera of patients with multiple sclerosis — association with chronic progressive disease course?

Multiple sclerosis (MS) is widely accepted as a systemic T- cell-mediated autoimmune disease with a T-helper type-1 (TH-1) profile of cytokine production. We addressed the question whether interleukin-12 (IL-12), as a central mediator of TH-1-cell activities, is detectable in sera of MS patients, and if there is any association with disease activity. We analysed 171 sera of patients with MS and meningitis, and healthy controls. IL-12 p40 protein was detectable at low levels in MS patients (median 43 pg/ml) and controls (median 49 pg/ml). Analysing different disease courses and activities, a significant elevation in stable primary progressive MS cases compared with controls (median 66 pg/ml) was found. IL-12 p40 protein was not detectable in cerebrospinal fluid probes of 10 patients. We conclude that the function of IL-12 in MS depends on expression and degradation of the different proteins. These could act proinflammatory as well as limiting the disease process. Copyright Lippincott Williams & Wilkins     

Interferon beta induces T-helper 2 immune deviation in MS

OBJECTIVE: To define the in vitro effects of interferon beta la (IFN-beta1a) on myelin basic protein (MBP)-reactive T cells and to determine its regulatory mechanism on cytokine networks in patients with MS. METHODS: The proliferation and cytokine production of MBP-reactive T-cell clones were measured in thymidine uptake assays and ELISA respectively. The precursor frequency of MBP-reactive T cells was estimated in a microwell culture system. RESULTS: IFN-beta inhibited the proliferation of established MBP-reactive T-cell clones, which correlated with enhanced production of anti-inflammatory interleukin (IL)-4 and IL-10, and a decrease in tumor necrosis factor alpha (TNF-alpha) and IFN-gamma. When examined with peripheral blood mononuclear cells (PBMCs), IFN-beta was found to reduce the in vitro T-cell responses to MBP, as indicated by the significantly decreased frequency of MBP-reactive T cells. The decreased frequency of MBP-reactive T cells corresponded to an augmented production of IL-4 and IL-10. Although the level of TNF-alpha and IFN-gamma was generally unaltered or decreased, IFN-beta appeared to enhance the production of IFN-gamma in PBMCs derived from some individuals with MS. CONCLUSION: Interferon beta la (IFN-beta) suppresses myelin basic protein (MBP)-reactive T cells and induces immune deviation toward the production of T-helper 2 cytokines, which may contribute to its therapeutic benefit in MS. The study also suggests some heterogeneity in MBP-reactive T-cell responses to IFN-beta in different individuals with MS.     

Molecular evidences for a role of HSV-1 in multiple sclerosis clinical acute attack

To verify the possible role of human herpesviruses as triggering or aggravating factors in relapsing-remitting multiple sclerosis (RRMS) clinical acute attack, we studied the prevalence of some herpesviruses in the peripheral blood mononuclear cells (PBMCs) collected from 22 MS patients during an MS relapse and in a stable phase and from 18 healthy controls (HC). DNA belonging to Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), Human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and Human Herpes virus 6 (HHV-6) has been searched by specific nested polymerase chain reaction (n-PCR). EBV and HHV6 DNA has been detected with high frequency in acute and stable MS and in healthy controls without significant differences. HCMV DNA was observed both in acute and stable MS but not in HC, and, more interestingly, HSV-1 DNA was only found in 13% of acute MS, while both stable MS and healthy controls were negative. On the basis of these results we focused on HSV-1, and to confirm them and to demonstrate that HSV-1 is actively replicating in MS patients during clinical relapse, we searched both messenger RNA (mRNA) and DNA of HSV-1 in the PBMCs of 15 acute MS patients and 15 healthy controls. We found HSV-1 mRNA and DNA in a significant number of acute MS patients but not in the control group. On the whole these data indicate that HSV-1 reactivate in the peripheral blood of MS patients during clinical acute attack and probably play a role in the triggering of MS relapses.     

Brain-derived neurotrophic factor in patients with multiple sclerosis

The aim of the present research was to verify the production of BDNF by peripheral blood mononuclear cells (PBMCs), unstimulated and stimulated with phytohemagglutinin (PHA), anti-OKT3 Ab and myelin basic protein (MBP), in 35 patients affected by multiple sclerosis (MS), 20 with relapsing-remitting (R-R) MS and 15 with secondary progressive (SP) MS. Seven R-R MS patients were assessed during the attack, in the subsequent recovery phase and also 3 months after relapse. The production of BDNF by PBMCs was also evaluated in 20 age- and sex-matched control subjects. Levels of BDNF were also determined in CSF of both patient groups and 20 control subjects. RESULTS: Levels of BDNF (pg/ml) in the supernatants of unstimulated and PHA-, anti-OKT3 Ab- and MBP-stimulated PBMCs in patients with R-R MS were significantly higher during relapse and in the recovery phase compared with values detected in the stable phase of the disease. Significantly lower BDNF values were found in unstimulated and stimulated PBMC supernatants of patients with SP MS compared to control subjects. This reduction was greater in patients with a 1-point increase in the EDSS score in the last 6 months compared with that in patients without a progression of the disability score. Reduction in the levels of BDNF was also confirmed in the CSF of SP MS patients compared with R-R MS patients assessed during a stable phase of the disease and control subjects. DISCUSSION: On the basis of recent experimental findings, a neuroprotective effect of BDNF produced by inflammatory cells can be hypothesized during relapses in MS. This can favor remyelination. The reduced production of BDNF by PBMCs of patients with SP MS can contribute to the progression of demyelinating disease and axonal loss in this form.     

Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease

OBJECTIVE: To evaluate the expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). BACKGROUND: MS is an immune-mediated disease and cytokines hove been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. METHODS: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4+ and CD8+ T MS patients express significantly more CD4+ and CD8+ T cells were analyzed for IFN-gamma, IL-2, TNF-alpha, IL-4, IL-10 and IL-13 production. RESULTS: cells producing IFN-gamma compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4+ T cells producing IL-2, IL-13 and TNF-alpha and a significant increase in CD8+ T cells producing IL-4 and IL-10. CONCLUSIONS: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.     

IFN-beta1a and IFN-beta1b have different patterns of influence on cytokines

Multiple sclerosis is characterized by elevated levels of proinflammatory cytokines produced by Th1 cells and decreased levels of anti-inflammatory cytokines produced by Th2 cells. IFN-beta treatment shifts the immune response from the Th1 to Th2 pattern, thus enhancing the production of anti-inflammatory Th2 cytokines such as IL-4, IL-10, and decreasing the production of proinflammatory Th1 cytokines such as IFN-gamma. To determine which IFN-beta has the stronger immunomodulatory effect we compared the levels of IL-4, IL-10, and IFN-gamma of 12 relapsing-remiting MS patients treated with IFN-beta1b (Betaferon) with those of 10 patients treated with IFN-beta1a (Avonex). There were no statistically significant differences in duration of disease, number of relapses before and during treatment, and in EDSS after 2 years of treatment. After 1 year of treatment the concentration of IFN-gamma was significantly lower in the Betaferon group, and concentrations of IL-4 and IL-10 were significantly higher in the Avonex group. It appears that IFN-beta1b has a downregulatory effect on both Th1 and Th2 cytokines, while IFN-beta1a causes a shift of the cytokine profile toward the Th2 phenotype. These two IFN have different influences on the pattern of cytokines in MS: IFN-beta1a enhances the production of anti-inflammatory cytokines IL-4 and IL-10 and IFN-beta1b decreases the production of the proinflammatory cytokine IFN-gamma.     

Pro- and anti-inflammatory cytokine gene polymorphism profiles in Bulgarian multiple sclerosis patients

Dysregulation in the expression of pro- and anti-inflammatory cytokines is one of the milestones in multiple sclerosis (MS) development and progression. The aim of this study was to investigate the possible influence of TNF-alpha (-308), TGF-beta (codons 10 and 25), IL-10 (-1082, -819, -592), IL-6 (-174) and IFN-gamma (+874) polymorphisms on susceptibility to multiple sclerosis (MS). Genotyping was performed by PCR-SSP method in 55 MS patients with relapsing-remitting form of the disease and 86 healthy subjects from Bulgarian population. We observed a statistically significant increase in the CC genotype of IL-10 -819 and -592 SNPs coupled with a decreased frequency of the TGF-beta +915 CG genotype in our MS patients (Pc<0.05). No significant differences were observed between MS patients and controls with respect to the distribution of the other cytokine gene polymorphisms investigated. Although the size of the study group is small, these results indicate that polymorphic variations of two of the major anti-inflammatory cytokines, IL-10 and TGF-beta, may play a role in MS susceptibility.     

Impaired interleukin-12 production in multiple sclerosis patients.

Multiple Sclerosis (MS), a disease of the human central nervous system, is believed to be a T cell mediated autoimmune disorder with genetic and environmental influences. Interleukin-12 (IL-12), a proinflammatory cytokine produced primarily by antigen presenting cells is a potent inducer of interferon-gamma (IFN-gamma) and other Th1 cytokines that may play an important role in MS pathogenesis. We have investigated IL-12 production induced by the T cell independent pathway in untreated and IFN-beta treated MS patients, healthy individuals and other neurological disease (OND) patients in response to the human pathogen Staphylococcus aureus. We report that peripheral blood mononuclear cells (PBMC) from untreated MS patients produce normal amounts of the biologically active IL-12 p70 heterodimer but significantly less free IL-12 p40 heavy chain than PBMC from both healthy and disease controls when challenged in vitro with Staphylococcus aureus. Both mRNA expression of the inducible IL-12 p40 chain and protein levels were found to be reduced in untreated MS patients. No decrease in the production of the IL-12 p40 was seen in MS patients on IFN-beta therapy. The decreased production of IL-12 p40 heavy chain is not attributed to increased IL-10 secretion, a defect in the production of cytokines by macrophages or the number of cytokine producing cells. The factor(s) responsible for the decrease in p40 remain to be determined. Since IL-12 p40 antagonizes the biological activity of IL-12 in vitro and in vivo, identification of a defect in the 'natural' antagonist of IL-12, may provide the basis for immune therapy.     

Increased serum levels of interleukin-18 in patients with multiple sclerosis

Serum but not CSF concentrations of the interferon-gamma-inducing cytokine interleukin (IL)-18 were significantly augmented in patients with MS as compared to both healthy controls and patients with other neurologic diseases. Patients with MS with secondary chronic progressive disease had significantly higher serum levels than those with relapsing remitting MS. In the latter group, IL-18 levels were higher in patients with acute exacerbation as compared to those with stable disease.     

Interferon gamma responses to myelin peptides in multiple sclerosis correlate with a new clinical measure of disease progression

The relationship between autoreactivity to myelin antigens and disease progression in multiple sclerosis (MS) is not fully understood. We addressed this relationship by cross-sectionally comparing an objective measure of MS disability with immune cytokine responses to myelin proteins. The ELISPOT assay was used to determine the ex vivo interferon gamma (IFNgamma) and interleukin-10 (IL-10) production by peripheral blood mononuclear cells (PBMCs) in response to peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in 20 patients with relapsing-remitting (RR) MS and 27 age- and sex-matched healthy controls. MS patients showed significantly higher MBP-induced IFNgamma responses and PLP-induced IL-10 responses compared with healthy controls. Using the Multiple Sclerosis Functional Composite (MSFC), a new multifactorial measure of disability, MS patients showed a significant correlation between the IFNgamma response to PLP peptides and MBP peptides, and disability. In contrast, in MS patients, there was no correlation between the MSFC and the response to unrelated control antigens or mitogens. These data show that myelin-specific T lymphocytes secreting the inflammatory cytokine IFNgamma correlate with functional impairment in MS, supporting an antigen-specific link between the immune response to myelin and disability in MS.     

Inhibition of lipopolysaccharide stimulated interleukin-1beta production after subarachnoid hemorrhage

PURPOSE: To identify the characteristics of cytokine production from peripheral blood mononuclear cells (PBMCs) in response to lipopolysaccharide (LPS) in patients with subarachnoid hemorrhage (SAH). METHODS: Blood samples were collected on the first day and 3 days after SAH (n = 12) to measure plasma concentrations of catecholamines, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-10. PBMCs from SAH patients or healthy volunteers were incubated with LPS (1 microg) for 24 hours. In the second phase, PBMCs from healthy volunteers (n = 6) were incubated with or without catecholamine (10 micromol/1) for 6 hours. After pre-treatment, the cells were treated with LPS (1 microg) for 18 hours. Supernatants were extracted and subjected to measurement by enzyme-linked immunosorbent assay. RESULTS: Plasma concentrations of epinephrine or dopamine prolong increased significantly 3 days after SAH, involved in elevation of plasma IL-10. In the PBMCs from the SAH patients, LPS-stimulated IL- 10 production was inhibited significantly. Pre-treatment with epinephrine or dopamine inhibited LPS-stimulated IL-1beta production significantly in the PBMCs from the healthy volunteers. CONCLUSIONS: The initial SAH involved in an impaired production of pro-inflammatory cytokines in response to LPS with an elevation of plasma epinephrine, dopamine and IL-10 after acute stressful conditions. This phenomenon may play an important role of an early immnosupression in patients with poor grade SAH.     

Cytokine production by peripheral blood monocytes/macrophages in the patients with multiple sclerosis and its suppression by methylprednisolone]

The production of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by stimulated peripheral blood monocytes/macrophages (PBM) was assessed in patients with multiple sclerosis (MS), other neurological diseases (OND) or normal controls (NC) using enzyme-linked immunosorbent assay (ELISA). PBM obtained from acute phase of MS produced significantly higher amount of all these cytokines than those from chronic stable MS, OND or NC (TNF alpha, IL-1 alpha, IL-6: p less than 0.01, IL-1 beta: p less than 0.05). Methylprednisolone (MP) inhibited the lipopolysaccharide-induced cytokine production in a dose-dependent manner. These results suggest the possible roles of activated monocytes/macrophages in the acute exacervation of MS and suppressive effect of MP on cytokine production by activated monocytes/macrophages.     

Pattern of cytokine secretion by peripheral blood cells of patients with multiple sclerosis in Brazil

Autoimmune T cells play a key role as regulators and effectors of organ-specific autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components produce a plethora of inflammatory cytokines and mediators that contribute to myelin damage. The production of proinflammatory and regulatory cytokines by peripheral blood cells from patients with active and stable MS and healthy controls were examined. The results show that TNF alpha production was somewhat elevated in active MS with no significant increase in the level IFN gamma, whereas in the chronic phase the anti-inflammatory cytokines IL-10 and TGF beta increased, accompanied by a reduction in IFN gamma when stimulated by myelin basic protein. Multiple Sclerosis (2000) 6 293 - 299