Plasma and cerebrospinal fluid activities of tissue plasminogen activator, urokinase and plasminogen activator inhibitor-1 in multiple sclerosis

Objective: To study plasma and cerebrospinal fluid (CSF) levels of tissue plasminogen activator (tPA), urokinase (UPA) and plasminogen activator inhibitor-1 (PAI-1) in multiple sclerosis (MS) patients. Design: Patients diagnosed as, or suspected of having, MS were involved in this study. The reference subjects had lumbar punctures for clinical reasons but were exclusive of having either MS or other types of neurological diseases. The identities of MS and reference samples were unknown to the researcher until laboratory results were ready. Setting: Department of Neurology, University of Helsinki, Finland. Subjects and Methods: tPA, uPA and PAI-1 levels were studied by an immunocapture assay, zymography and enzyme immunoassay in 19 patients with MS and 20 reference subjects. Results: Samples were qualitatively screened for both tPA and uPA activity by zymography and positive samples were quantitated. We observed significantly higher mean levels of CSF tPA (MS: 360+/-24 mlU/ml, REF: 43.7+/-6 mlU/ml; P < 0.001) and PAI-1 (P = 0.048) in patients with MS, in comparison with the reference subjects. Plasma PAI-1 and tPA values were within reference ranges in the patients. Although the CSF tPA activity correlated positively with age in the reference subjects (P = 0.011; r = 0.61), no correlation was observed in MS. There was no association between the CSF PAI-I and age either in the patients or the reference subjects. Nine of 19 CSF samples and 6 of 8 plasma samples of MS patients had quantifiable uPA activity, whereas reference samples did not. Conclusions: CSF tPA activity appears raised in MS patients. The assessment of tPA activity and its specific inhibitor may be useful for understanding the pathogenesis/prognosis of MS and similar neurological diseases.