Tumor Necrosis Factor-alpha (TNF-) is a peptide that is derived from T-Lymphocytes and Macrophages and is used as a marker of activated Cellular Immune Responses.

TNF- was measured in paired Sera and CerebroSpinal Fluid (CSF) from 30 patients with Multiple Sclerosis (MS) with worsening disability, 54 patients with other neurological diseases, and 20 normal subjects.

A sensitive enzyme-linked Immunosorbent assay was used to determine the TNF- levels.

We found significantly elevated Serum and CSF levels in 12 (40%) and 6 (20%) MS patients, respectively, compared with healthy controls (P < 0.007 and P < 0.05).

Among the 18 patients with neuropathy, we also found high Serum and CSF TNF- values in 3 (17%) and 5 (28%) patients, respectively (P < 0.04 and P < 0.002).

Our study shows that TNF- is probably involved in the PathoGenetic mechanisms of MS and other Inflammatory Neurological Diseases.

Concentrations of InterLeukin (IL)-12 and Tumor Necrosis Factor-alpha (TNF-) in CerebroSpinal Fluid (CSF) were measured in patients with Multiple Sclerosis (MS) and control patients with non-inflammatory neurological diseases (NIND) by an enzyme-linked Immunosorbent assay.

TNF- was detectable in the CSF of 60% of the patients with active MS, none of those with inactive MS and 29% of patients with NIND.

CSF concentrations of TNF- correlated with the degree of disability in MS patients (P < 0.05). Detectable levels of IL-12 were found in 10% of the MS CSF samples and 18% of NIND CSF samples.

There was a significant relationship between CSF concentrations of IL-12 and those of TNF- in MS patients (P < 0.05); no relationship was observed between the presence of IL-12 and disease activity or severity.

These findings further stress the involvement of T-helper 1 type-response within the Central Nervous System in MS.

We studied Interferon-gamma (IFN-), --Tumor Necrosis Factor (--TNF) and Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) in the CerebroSpinal Fluid and Serum of 18 patients with Multiple Sclerosis (MS) and 10 subjects with Other Neurological Diseases (OND).

We also studied the CerebroSpinal-Fluid CD 69 expression, and T-Cells with T-Cell Receptor (TcR) /delta+.

We found an increase of IFN- (14.0 +/- 3.5 U/ml) and GM-CSF (8.0 +/- 3.4 pg/ml) levels in the CerebroSpinal Fluid of MS patients compared to the OND group (p < 0.005 and p < 0.01, respectively).

The frequency of detectable CerebroSpinal-Fluid and Serum --TNF was similar in patients with MS and with OND.

The CerebroSpinal-Fluid CD69 expression in Lymphocytes was significantly higher in MS patients (15.0 +/- 9.9%) than in the control group (3.7 +/- 6.2%; p < 0.005).

Comparable Serum levels of IFN- and GM-CSF were detected in patients with MS and in OND subjects. No significant difference in the incidence of TcR /delta+ in the CerebroSpinal Fluid was found between the two groups.

These results indicate an activation of T-Lymphocytes and Macrophages in patients with MS. Our data do not suggest a role for an increased incidence of TcR /delta+.

However, we cannot rule out the possibility that these T-Cells could be present at the plaque site of MS patients.

Magnetic Resonance Imaging of Multiple Sclerosis (MS) patients often shows active inflammatory lesions despite clinical remission. No Immunological marker of disease activity has been identified in these patients.

Concentrations of Neopterin, InterLeukin-2 (IL-2), soluble InterLeukin-2 receptor (sIL-2R) and Tumor Necrosis Factor- (TNF-) were measured in the Serum and CerebroSpinal Fluid of 19 clinically-inactive MS patients and compared with those of 19 non-inflammatory controls.

CerebroSpinal Fluid (CSF) Neopterin concentrations were significantly higher in the MS group than in controls (mean 9.1 mM vs 3.4 nM, P < 0.01) and 10 of 19 MS patients had levels above the control range.

This finding provides evidence of ongoing T-Cell-directed and Interferon-gamma-mediated Macrophage activation in the Central Nervous System. Analysis of IL-2, sIL-2R and TNF- concentrations revealed no significant differences between MS patients and controls.

We conclude that CSF Neopterin concentration may correlate with disease activity in asymptomatic patients.

T-Cell clones derived from the CSF (CerebroSpinal Fluid) of MS (Multiple Sclerosis) patients have been analyzed for the production of Interferon-gamma (IFN-), Tumor Necrosis Factor- (TNF-), InterLeukin-2 (IL-2) and InterLeukin-4 (IL-4).

Each CSF-T clone (both CD4⁺ and CD8⁺) produced substantial amounts of IFN- and especially TNF- compared with autologous peripheral T clones and Liver-infiltrating T clones from patients with chronic active Hepatitis.

The large quantities of TNF produced by CSF-T-Cell clones suggest an important role for this Cytokine in MS ImmunoPathoGenesis.

AntiBodies to an Axolemma-enriched fraction (AEF) Antigen have been detected in the CerebroSpinal Fluid (CSF) and Serum of patients with Multiple Sclerosis (MS) using an enzyme-linked Immunosorbent assay (ELISA).

A marginal elevation (P < 0.08) of anti-AEF IgG was found in MS CSF when compared with OND samples. When CSF was diluted to a standardized IgG concentration, the anti-AEF IgG level in MS CSF was significantly elevated (P=0.007) when compared to OND CSF.

MS Serum was also found to contain a significantly higher level (P < 0.001) of anti-AEF IgG when compared to OND Serum using the ELISA technique.

InterLeukin (IL) 1 ß, Tumor Necrosis Factor - (TNF-), and IL-6 are Cytokines which mediate cellular responses during Immune activation and inflammation.

In Multiple Sclerosis (MS) they might be responsible for T-Cell activation (IL-1 ß), for DeMyelination (TNF-), and for ImmunoGlobulin (Ig) synthesis (IL-6) within the Central Nervous System.

We studied IL-1 ß, TNF-, and IL-6 levels in the CerebroSpinal Fluid (CSF) of 34 patients with MS, 43 patients with Non-Inflammatory Neurological Diseases (NIND), and 19 patients with Inflammatory Neurological Diseases (IND). IL-6 was found in the CSF of 29% of MS, 7% of NIND, and 47% of IND patients.

TNF- was detected in the CSF of 23% of MS, 7% of NIND, and 29% of IND. CSF IL-6 and TNF- levels were significantly higher in MS and IND than in NIND. IL-1 ß was rarely detected in the CSF of any group.

At least one Cytokine was detected in 52% of MS CSF, 11% of NIND CSF, and 64% of IND CSF. In MS patients, no relationship was observed between the incidence or the amount of Intrathecal IgG synthesis or Oligoclonal Bands and the presence of any Cytokine.

We also evaluated Cytokine levels in paired Sera from 11 MS and 13 NIND patients. Low levels of IL-6 were detected in most Sera from MS and NIND patients. TNF- was detected in only two MS sera, and IL-1 ß was undetectable in any sample.

Our results indicate that increased CSF levels of the Cytokines IL-6 and TNF- occur frequently in MS and IND, but there is no obvious relationship to Intrathecal Ig synthesis.

The CerebroSpinal Fluid (CSF) IgG index, the CSF to Serum Albumin Ratio, and electrophoresis on agarose gel of CSF and Serum were evaluated retrospectively for their usefulness in the differential diagnosis of Multiple Sclerosis (MS).

Standardized procedures were adopted for grading the intensity of OligoClonal Banding and for the certainty of diagnosis of MS.

One hundred and forty-nine patients were studied including:
1. 23 with Definite Multiple Sclerosis (MS)
2. 12 with Probable MS
3. 20 with Possible MS
4. 20 with Inflammatory Neurologic Disease
5. 65 with Noninflammatory Neurologic Disease
6.   9 with No Neurologic Disease

The CSF IgG index and the CSF to Serum Albumin Ratio were calculated from nephelometric measurements of Serum and CSF IgG and Albumin.

The intensity of OligoClonal Banding was graded relative to the density of the Pre-Albumin Band. Eighty-eight per cent of cases of Definite MS had distinct OligoClonal Bands, and an equal number had an elevated IgG Index.

These tests were not specific for MS, however, since 50% of cases of Inflammatory Neurologic Disease and 5% of those with Noninflammatory Neurologic Disease had an elevated IgG Index.

Similarly, 48% of cases with Inflammatory Disease and 25% with NonInflammatory Disease had OligoClonal Bands.

However, only patients with Definite MS (21%) or Possible MS (4%) had prominent OligoClonal Bands whose density was greater than or equal to that of PreAlbumin, together with a CSF IgG Index greater than 1.50.