Antonis Rombos

IL-15 is elevated in serum and cerebrospinal fluid of patients with multiple sclerosis.

UNLABELLED Interleukin-15 (IL-15) is a novel proinflammatory cytokine having similar biological activities to IL-2 which is implicated in the pathogenesis of multiple sclerosis. It is produced by activated blood monocytes, macrophages and glial cells. There is little information about the involvement of IL-15 in the development of multiple sclerosis (MS). The objective of our study was to measure IL-15 serum and cerebrospinal fluid (CSF) levels in MS patients and to correlate serum and CSF IL-15 concentrations with clinical parameters of the disease. CSF IL-15/Serum IL-15 ratio (c/s IL-15 ratio) was introduced to assess the origin of elevated IL-15 levels. MATERIALS AND METHODS We measured serum and CSF IL-15 levels in 52 patients with MS and 36 age and gender matched patients with inflammatory (IND) and non-inflammatory neurological diseases (NIND) studied as control groups. IL-15 levels were correlated with clinical parameters as duration, disability, MRI activity and clinical subtypes of the disease. RESULTS MS patients were found to have significantly higher serum IL-15 levels compared with IND (p=0.00016) and NIND patients (p=0.00045). Elevated levels of IL-15 were also found in CSF samples from MS patients compared with patients with IND (p=0.00034) and NIND (p=0.0003). Among MS subgroups there were no statistically different IL-15 serum and CSF concentrations. No significant correlation of serum and CSF IL-15 concentrations with MRI activity, disability assessed by EDSS score and duration of the disease were also found. C/S IL-15 ratio was found lower in MS patients compared with IND (p=0.01) and not significantly different compared with NIND patients (p=0.14) suggesting that systemic activation might be the source of high CSF IL-15 levels in MS patients. CONCLUSIONS Our findings suggest a possible role of IL-15 in the immunopathogenetic mechanisms of MS.

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.

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 Alzheimers 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.

The role of soluble intercellular adhesion molecules in neurodegenerative disorders.

UNLABELLED Immunological disturbances have been implicated in the pathogenesis of some neurodegenerative disorders like Alzheimers disease (AD) and amyotrophic lateral sclerosis (ALS). Adhesion molecules are markers of activated endothelial cells upregulated by action of cytokines. MATERIALS AND METHODS To investigate the activation or not of the vascular cells in AD and ALS, serum soluble intercellular adhesion molecule-1 (ICAM-1) and soluble E-selectin were evaluated (enzyme-like immunosorbent assay, ELISA) in 22 patients with Alzheimers disease (AD), 20 patients with amyotrophic lateral sclerosis (ALS), 34 patients with non-inflammatory neurological diseases (NIND) and 15 control subjects. RESULTS Patients with AD had higher s-ICAM-1 levels compared to NIND patients and control subjects (p<0.0027 and p<0.04, respectively). Patients with ALS had not higher s-ICAM-1 levels compared to NIND patients and control subjects (p<0.21 and p<0.31, respectively). Soluble-E-selectin levels in AD and ALS patients were not statistically different compared to NIND patients and controls (p<0.4, p<0.9 and p<0.3, p<0.19, respectively). CONCLUSIONS The presence of high s-ICAM values may be related to immunological processes involved in pathogenetic mechanisms of AD. The not statistically significant values of s-E selectin, a glycoprotein considered an exclusive marker of endothelial activation, seem to suggest the neural rather than the endothelial s-ICAM origin in patients with AD. The low values of s-ICAM-1 and sE-selectin in the serum of ALS patients do not exclude the presence of an unconventional immunological abnormality in this disorder.

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.

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.

Serum levels of soluble intercellular adhesion molecule-1 (s-ICAM-1) and soluble endothelial leukocyte adhesion molecule-1(s-ELAM-1) in amyotrophic lateral sclerosis

Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Adhesion molecules are markers of activated endothelial cells up-regulated by action of cytokines. To investigate the activation or inactivation of the vascular cells in ALS, serum soluble intercellular adhesion molecule-1 (s-ICAM-1) and soluble E-selectin (s-ELAM-1) were evaluated (ELISA) in 16 patients with ALS, 30 patients with non-inflammatory neurological diseases (NINDS) and 15 healthy control subjects. Patients with ALS had no higher s-ICAM-1 levels compared with the NINDS patients and the control subjects (p<0.31 and p<0.21, respectively). s-ELAM levels were not statistically significant compared with the NINDS patients and healthy subjects (p<0.21 and p<0.24, respectively). We conclude that the low values of s-ICAM-1 and s-ELAM-1 in the serum of ALS patients do not exclude the presence of immunological abnormality in this disorder. Soluble E-selectin is a glycoprotein which is considered an exclusive marker of endothelial activation. Its low level in our study may suggest a neural rather than an endothelial s-ICAM origin in patients with ALS.

Proinflammatory cytokines in serum and cerebrospinal fluid of CIDP patients

Abstract 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.

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

Abstract 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.