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 necrosis factor-alpha (TNF-alpha) can cause myelin damage and contribute to MS pathogenesis. We measured plasma and cerebrospinal fluid (CSF) levels of TNF-alpha and its soluble receptors, TNF-sRp55 and TNF-sRp75, in 18 patients with active MS, and in neurological and healthy controls. The same determinations were repeated on plasma and on CSF samples that were collected after the MS patients had ended a six-day treatment with high-dose methylprednisolone (MP). Pre- and post-treatment plasma and CSF TNF-alpha levels, when detectable, 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 controls. Post-treatment CSF TNF-sRp55 levels were higher than in the active phase of the disease. The MS patients, who clinically improved, tended to have the highest CSF TNF-sRp55 levels. The increase was due to intrathecal TNF-sRp55 synthesis. Although it is involved in MS pathogenesis, TNF-alpha is not detectable in plasma or in CSF samples from MS patients in various phases of the disease. A better marker of disease activity seems to be CSF TNF-sRp55 levels. The increased CSF levels of TNF-sRp55 in response to MP circumstantially suggest that this receptor could partially account for the beneficial effects of MP in acute MS.
Franciotta
D
D
Neurological Institute "C. Mondino Foundation", via Palestro 3, I-27100 Pavia, Italy. francid@mondino.it
Bergamaschi
R
R
Martino
G
G
Zardini
E
E
Desina
G
G
Cosi
V
V
D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000378:metabolism*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone