J Neurol (2001) 248 : 487– 495 © Steinkopff Verlag 2001 ORIGINAL COMMUNICATION G. Giovannoni D.H. Miller N.A. Losseff M. Sailer N. Lewellyn-Smith A.J. Thompson E.J. Thompson Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis JON 456 ■ Abstract The aim of this study was to assess whether mean serum levels of inflammatory markers when measured serially correlate with disease progression or puta- tive MRI markers of axonal loss in a cohort of well-characterised mul- tiple sclerosis (MS) patients. Serial serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion mol- ecule-1 (sICAM-1), nitric oxide Received: 14 August 2000 Received in revised form: 8 December 2000 Accepted: 30 December 2000 Dr. G. Giovannoni () · N. Lewellyn-Smith · E.J. Thompson Departments of Neurochemistry University of London Queen Square London WC1N 3BG, UK Tel.: +44-20-78 37-36 11 Fax: +44-20-78 37-85 53 e-mail: G.Giovannoni@ion.ucl.ac.uk G. Giovannoni · D.H. Miller · A.J. Thompson Department of Clinical Neurology University College, London D.H. Miller · N.A. Losseff · M. Sailer · A.J. Thompson NMR Research Unit Institute of Neurology University College London metabolites nitrate and nitrite (NO x ), C-reactive protein (CRP), neopterin and tumour necrosis fac- tor alpha (TNF-α) were measured in 29 MS patients, 13 with a relaps- ing remitting (RR) and 16 with a secondary progressive (SP) course, who were participating in a phase II clinical trial of anti-CD4 therapy. Short-term whole blood stimulated TNF-α production was also mea- sured. Patients were studied 12 times over an 18-month period. MRI variables included the number and volume of Gd-enhancing le- sions and the change in T2-hyper- intense, T1-hypointense lesions and cerebral volume between the baseline and exit studies. Disease progression required a sustained change in the EDSS. There was no correlation between mean levels of inflammatory markers over the study period and disease progres- sion or changes in any of the MRI measures. However, mean sICAM-1 levels from the first 6 months of the study were higher in patients who progressed during the study than in those that did not (443 (SD439) vs. 235 (SD162) ng/mL, p=0.05). Mean levels of NO x were signifi- cantly higher in patients with RR MS than in patients with SP disease (59.1μmol/L (SD 12.8) vs. 48.7μmol/L (SD 11.9), p=0.02). Patients with either a single relapse or no relapse had significantly higher NO x levels than to patients with multiple relapses during the 18 month follow-up (59.0μmol/L (SD 12.3) vs. 47.9μmol/L (SD 12.0), p=0.02). The mean levels of the other inflammatory markers did not correlate with disease course or relapse-rate. Serum levels of many inflammatory markers do not correlate with short-term disease progression. Some of the data suggest that the effects of inflam- mation on disease progression are delayed. In addition raised levels of serum nitric oxide metabolites are associated with a lower number of clinical relapses and a non-pro- gressive disease course. These find- ings, although preliminary, pose interesting questions on the role of nitric oxide in the pathogenesis of MS. Inducible NO production in the early stages of the disease may be beneficial. ■ Key words Nitric oxide · Multiple sclerosis · Cerebral atrophy · Hypointense lesions · Disease progression