Proinflammatory cytokines in serum and cerebrospinal fluid of CIDP patients.

INTRODUCTION: Little is known about the role of cytokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Interleukin (IL)-12 and IL-15 are the major growth and differentiation factors for Th-1 cells and IL-17 is a marker of Th-17 cell expansion and activation, a high proinflammatory new subset of T cells that induce severe autoimmunity. PATIENTS AND METHODS: We measured by enzyme-like immunosorbent assay serum and cerebrospinal fluid (CSF) levels of IL-15, IL-12, and IL-17 in 24 patients with CIDP and 12 patients with other non-inflammatory neurological disorders and serum levels in 16 healthy subjects. RESULTS: We found a positive association of CSF IL-12 (P = 0·012) with CIDP presence (P<0·001). CONCLUSIONS: Our findings suggest that IL-12 may be involved as potential marker of immune activation in CIDP. The increase in its levels in CSF may be a marker of initiation of Th-1 cell-mediated immunity.

Stress management and multiple sclerosis: a randomized controlled trial.

There is a well-established adverse reciprocal relationship between stress and multiple sclerosis (MS). However, stress management in these patients has been parsimoniously studied. In this parallel randomized controlled trial, relapsing-remitting MS patients were randomly assigned to undergo either an 8-week stress management program (n=31; relaxation breathing and progressive muscle relaxation, twice a day) or not (n=30). Self-reported validated measures were used to evaluate perceived stress, health locus of control, anxiety, and depression. Daily diaries of MS symptoms were also kept by patients. In patients in the intervention group, perceived stress and symptoms of depression were significantly decreased after 8 weeks of relaxation. Repeated measures analyses showed significant group-by-time interactions for both the number of weekly symptoms and the mean intensity per symptom. No other significant change was reported. We deem that our results should encourage future studies that will incorporate more objective clinical and laboratory outcomes.

Interleukin-15 and interleukin-12 are elevated in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

BACKGROUND: There is evidence that immunological factors may be involved in pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). Interleukin (IL)-15 and IL-12 are proinflammatory cytokines produced by activated blood and glial cells. They promote T cell differentiation and proliferation. PATIENTS AND METHODS: We measured by ELISA serum and cerebrospinal fluid (CSF) levels of IL-15 and IL-12 in 21 patients with ALS and 19 patients with other noninflammatory neurological disorders (NIND) studied as a control group. IL-15 and IL-12 serum and CSF levels were also correlated with duration of the disease, the disability level determined using the revised ALS Functional Rating Scale and the clinical subtype of the disease onset in patients with ALS. RESULTS: IL-15 and IL-12 serum levels were higher in patients with ALS as compared with patients with NIND (p = 0.014 and p = 0.011, respectively). IL-15 and IL-12 CSF levels were also increased in patients with ALS (p = 0.011 and p = 0.005, respectively). IL-15 and IL-12 levels were not correlated with disease duration, disability scale or clinical subtype of the disease onset in ALS patients. CONCLUSIONS: Our findings suggest that these molecules may be involved in the pathogenic mechanisms acting as potential markers of immune activation in ALS.

Circulating interleukin-15 and RANTES chemokine in MS patients: effect of treatment with methylprednisolone in patients with relapse.

INTRODUCTION: Interleukin-15 (IL-15) is a proinflammatory cytokine. RANTES is a member of the beta chemokines subfamily with strong chemoattractant activity for T lymphocytes and monocytes. MATERIALS AND METHODS: We measured by enzyme-like immunosorbent assay (ELISA) serum levels of IL-15 and RANTES in 24 patients with MS in relapse, 27 patients with stable MS and 21 healthy subjects. Serum levels of IL-15 and RANTES were also measured before, 5 days and 1 month after onset of treatment with methylprednisolone i.v. RESULTS: IL-15 serum levels were higher in patients with relapse compared with patients in stable stage of the disease and healthy subjects (p=0.001 and p=0.008 respectively). RANTES serum levels were increased in patients with relapse and stable disease as compared to healthy subjects (p=0.01). IL-15 and RANTES levels were not decreased after treatment with corticosteroids. CONCLUSIONS: Our findings suggest a possible role of IL-15 and RANTES in MS. Treatment with methylprednisolone in relapse had no effect on serum IL-15 and RANTES levels.

Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease.

In Alzheimer's disease (AD), potassium channel abnormalities have been reported in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients were similar to healthy individuals, glutamate (1-1000 microM) failed to yield the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate), resulting in a 4-fold increase of resting channel activity. Specific agonist and antagonist data indicate that this abnormality is due to dysfunction of cognate group II mGluRs. Given that glutamate is present in plasma and that both mGluRs and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may account for the presence of immune-associated alterations in AD. Furthermore, if this aberration reflects a corresponding one in neural tissue, it could provide a potential target in AD pathogenesis.

Effect of treatment with methylprednisolone on the serum levels of IL-12, IL-10 and CCL2 chemokine in patients with multiple sclerosis in relapse.

OBJECTIVES: Interleukin-12 (IL-12), a proinflammatory cytokine produced by Th1 cells, and interleukin-10 (IL-10), a product of Th2 cells, are involved in the pathogenetic mechanisms of multiple sclerosis (MS). CCL2 chemokine expression is induced by Th2 cytokines and is decreased in MS relapse. The mechanisms responsible for the beneficial effects of IVmethylprednisolone in attacks are not clearly established and the duration of the effect of this treatment remains controversial. PATIENTS AND METHODS: We measured by enzyme-like immunosorbent assay (ELISA) serum levels of IL-12, IL-10 and CCL2 before, 5 days and 1 month after the initiation of treatment with IVMP in 20 patients with MS in relapse. RESULTS: A significant increase of IL-10 and decrease of CCL2 serum levels was observed (p=0.0028 and 0.045 respectively) five days after the onset of steroid treatment but not after one month. Steroid treatment had no influence in serum levels of IL-12. CONCLUSIONS: The clinical improvement of our MS patients with relapse following the treatment with methylprednisolone may be associated with an immediate but not a long-term modification of serum levels of IL-10 and CCL2. IL-12 may not be influenced by steroid treatment.

RANTES levels are elevated in serum and cerebrospinal fluid in patients with amyotrophic lateral sclerosis.

Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells. Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a C-C beta-chemokine with strong chemo-attractant activity for T-lymphocytes and monocytes. We examined serum levels of RANTES in 20 patients with amyotrophic lateral sclerosis (ALS), 14 patients with non-inflammatory neurological disorders (NIND) and 13 control subjects (CTRL) and cerebrospinal fluid (CSF) levels of RANTES in ALS and NIND group patients in order to investigate whether RANTES as index of immune activation is present in ALS patients. Patients with ALS had higher RANTES levels compared with the NIND patients and CTRL subjects (p = 0.005 and p = 0.02, respectively). CSF RANTES levels were also higher compared with the NIND patients (p = 0.007). No correlation of serum and CSF RANTES levels with disease duration was found. These results may suggest an activated microglia induced recruitment of peripheral inflammatory cells to sites of inflammation in ALS patients.

Circulating interleukin-15 in dementia disorders.

The objective of this study was to assess the role of interleukin-15 (IL-15) as a potential marker of immune reactions in patients with Alzheimer's disease and vascular dementia. The authors measured by immunoassay serum IL-15 levels in 20 patients with Alzheimer's disease and 15 patients with vascular dementia and compared them with serum IL-15 levels in 15 healthy subjects. The authors also studied the effect of treatment with acetylcholinesterase inhibitors (AChEI) on serum IL-15 levels. Patients with Alzheimer's disease were found to have significantly lower serum IL-15 levels compared with healthy subjects and patients with vascular dementia. Healthy subjects and patients with vascular dementia did not differ between each other. Age, sex, disease duration, and Mini-Mental State Examination score did not affect IL-15 levels in any of the groups. Treatment with AChEI had no influence on IL-15 concentrations. The findings suggest that IL-15 is not implicated in the pathogenetic mechanisms of Alzheimer's disease and vascular dementia. An immune hyporesponsiveness at some point during disease development may be responsible for the lower levels of IL-15 and other cytokines in Alzheimer's disease patients.

Interleukin-12 is reduced in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

UNLABELLED: Interleukin-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines, such as Interferon-gamma and Tumor Necrosis Factor-alpha. There is little information about the involvement of IL-12 in the pathophysiology of Alzheimer's disease (AD) and other tauopathies. OBJECTIVES: The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with AD and frontotemporal dementia (FTD). PATIENTS AND METHODS: We measured by immunoassay cerebrospinal fluid (CSF) IL-12 levels in 19 patients with AD and 7 patients with FTD in comparison with CSF IL-12 levels in 30 patients with non-inflammatory neurological diseases served as neurological control patients (NCTRL). IL-12 levels were correlated with age, age of disease onset, disease duration, MMSE score, and rate of dementia progression. Abeta42 and Total tau (tau(T)) levels in CSF were also measured. RESULTS: Patients with AD had significantly lower CSF IL-12 levels compared with NCTRL patients (p<0.001). Patients with FTD had also lower CSF IL-12 levels compared with NCTRL patients (p<0.05). Age, sex, disease duration and MMSE score did not affect IL-12 levels in any of the groups. In AD a significant positive correlation was noted between IL-12 levels and tau(T) levels (Rs=0.46, p=0.048). CONCLUSIONS: Our findings may suggest a reduced inflammatory reaction during the course of AD and FTD. A neurotrophic role of IL-12 and other proinflammatory cytokines cannot be excluded.