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Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease

Department of Clinical Neurosciences and Division of Pathology and Infectious Diseases, Royal Free and University College Medical Schools, Rowland Hill Street, London NW3 2PF

N C Silver

Institute of Neurology, London WC1N 3BG

J O'Riordan

Institute of Neurology, London WC1N 3BG

R F Miller

Department of Clinical Neurosciences and Division of Pathology and Infectious Diseases, Royal Free and University College Medical Schools, Rowland Hill Street, London NW3 2PF

S J.R. Heales

Institute of Neurology, London WC1N 3BG

J M Land

Institute of Neurology, London WC1N 3BG

M Elliot

Kennedy Institute of Rheumatology, London W6 8LH

M Feldmann

Kennedy Institute of Rheumatology, London W6 8LH

D H Miller

Institute of Neurology, London WC1N 3BG

E J Thompson

Institute of Neurology, London WC1N 3BG

Nitric oxide (^•NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of .NO in the development of progressive disease we measured the .NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit: creat.urine) and neopterin (neopt: creat.urine) to creatinine ratios compared to NC subjects. (Median[25th-75th%] nit: creat.urine: NC=1183_[962-1365] vs DD=1245_[875-2403], AIDS=1686[1231-2531], and RA=1950[1214-2726] mmol/mol, P50.001 and median[25th-75th%] neopt: creat.urine: NC=99_[76-151] vs DD=163_[119-266], AIDS=972_[653-1456], and RA=389_[257-623] mmol/mol, P50.001). Patients with early DD and RR MS had significantly elevated nit: creat.urine compared to patients with progressive MS (nit: creat.urine: 1612[1020-2733] vs 1159_[790-1641] mmol/mol, P=0.006). The nit: creat.urine and neopt: creat.urine did not correlate with clinical relapse or MRI activity. Excretion of .NO metabolites is increased in patients with early or relapsing-remitting disease. .NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.

Key Words: urine • nitrate • nitrite • rheumatoid arthritis • HIV-1 • HIV-1 infection

Multiple Sclerosis, Vol. 5, No. 5, 335-341 (1999)
DOI: 10.1177/135245859900500506


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