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.
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.
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).
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.
- Comment in: N Engl J Med 1992 Jan 23;326(4):272-3