Tumor necrosis factor-alpha and its soluble receptors in plasma and cerebrospinal fluid of multiple sclerosis patients treated with methylprednisolone

Demyelination is the main pathological feature of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. Tumor necrosi s factor-alpha (TNF-alpha) can cause myelin damage and contribute to MS pat hogenesis. We measured plasma and cerebrospinal fluid (CSF) levels of TNF-a lpha and its soluble receptors, TNF-sRp55 and TNF-sRp75, in 18 patients wit h active MS, and in neurological and healthy controls, The same determinati ons were repeated on plasma and on CSF samples that were collected after th e MS patients had ended a six-day treatment with high-dose methylprednisolo ne (MP), Pre- and post-treatment plasma and CSF TNF-alpha levels, when dete ctable, and those of TNF-sRp75, did not vary, and were similar to those of controls. CSF TNF-sRp55 levels were higher in acute MS patients than in con trols. Post-treatment CSF TNF-sRp55 levels were higher than in the active p hase of the disease. The MS patients, who clinically improved, tended to ha ve the highest CSF TNF-sRp55 levels. The increase was due to intrathecal TN F-sRp55 synthesis. Although it is involved in MS pathogenesis, TNF-alpha, i s not detectable in plasma or in CSF samples from MS patients in various ph ases of the disease. A better marker of disease activity seems to be CSF TN F-sRp55 levels. The increased CSF levels of TNF-sRp55 in response to MP cir cumstantially suggest that this receptor could partially account for the be neficial effects of MP in acute MS.