Multiple Sclerosis Lesions 1

Background
Cachectin, or Tumor Necrosis Factor-alpha (TNF-), is a principal mediator of the Inflammatory response.

And may be important in the PathoGenesis and progression of Multiple Sclerosis, an Inflammatory disease of the Central Nervous System.

Methods
In a 24-month prospective study, we used a sensitive enzyme-linked Immunosorbent assay to determine levels of TNF-.

In CerebroSpinal Fluid and Serum in 32 patients with Chronic/Progressive Multiple Sclerosis and in 20 with stable Multiple Sclerosis and 85 with Other Neurologic Diseases.

An attempt was made to relate TNF- levels with the degree of disability of the patients with Multiple Sclerosis and with their Neurologic deterioration during the 24 months of observation.

Results
High levels of TNF- were found in the CerebroSpinal Fluid of 53 percent of the patients with Chronic/Progressive Multiple Sclerosis.

And in none of those with stable Multiple Sclerosis (P less than 0.001).

TNF- was detected in the CerebroSpinal Fluid of 7 percent of the controls (P less than 0.01) with other Neurologic disease.

In patients with Chronic/Progressive Multiple Sclerosis, mean TNF- levels were significantly higher in the CerebroSpinal Fluid than in corresponding Serum samples (52.41 vs. 11.88 U per milliliter; range, 2 to 178 vs. 2 to 39; P less than 0.001).

In these patients, CerebroSpinal Fluid levels of TNF- correlated with the degree of disability (r = 0.834, P less than 0.001) and the rate of Neurologic deterioration (r = 0.741, P less than 0.001) before the start of the study.

CerebroSpinal Fluid levels also correlated with the increase in Neurologic disability after 24 months of observation (r = 0.873, P less than 0.001).

Conclusions
These data provide evidence of Intrathecal synthesis of TNF- in Multiple Sclerosis.

And suggest that the level of TNF- in CerebroSpinal Fluid correlates with the severity and progression of the disease.

Our results suggest that TNF- may reflect histologic disease activity in Multiple Sclerosis and could be used to monitor outcomes or responses to therapy.

Multiple Sclerosis (MS) is a chromatic Inflammatory disease of the Central Nervous System, T-Lymphocytes play a major role in the PathoGenesis of the disease.

The exact mechanisms by which the Inflammation is regulated in MS have not yet been defined.

Studies in animal models of MS suggest that Apoptosis (Suicide) of T-Cells is the main factor terminating Inflammation.

The process of Apoptosis itself is regulated by a range of Pro- and Anti-Apoptotic proteins. The Bcl-2 Gene family is an important member of these proteins.

The present study investigated the expression of the Anti-Apoptotic protein Bcl-2 in 11 Chronic MS cases including five Relapsing/Remitting and six Chronic/Progressive MS patients.

A total of 35 lesions containing all stages of DeMyelinating activity were studied.

The number of CD 3-positive T-Cells and the absolute and relative numbers of T-Cell expressing Bcl-2 were determined by double ImmunoCytoChemistry.

Bcl-2 is expressed by T-Lymphocytes in MS plaques.

Patients with Chronic/Progressive MS have a higher proportion of Bcl-2 expressing T-Cells than patients with Relapsing/Remitting disease.

Highest numbers of Bcl-2-positive T-Lymphocytes were found in ReMyelinating and DeMyelinated lesions, whereas active DeMyelinating lesions revealed lower numbers.

These data indicate that cell-death-related proteins such as the Anti-Apoptotic protein Bcl-2 are expressed in MS lesions.

And that they might have important effects on the regulation of elimination or persistence of Inflammatory cells in the Central Nervous System.