DAILY URINARY NEOPTERIN EXCRETION AS AN IMMUNOLOGICAL MARKER OF DISEASE-ACTIVITY IN MULTIPLE-SCLEROSIS

The aim of this study was to assess neopterin, a marker of interferon gamma (IFN-gamma) induced macrophage activity as a possible surrogate marker of inflammation in patients with multiple sclerosis. Urinary ne opterin to creatinine ratios (UNCRs) were measured daily in 10 primary progressive (PP), 10 relapsing remitting (RR) and II secondary progre ssive (SP) patients with multiple sclerosis, and 14 normal control (NC ) subjects, for periods of up to 12 weeks. After excluding measurement s related to infection, the median of the individuals' average UNCRs w as significantly higher in patients than in controls (P < 0.001 for al l patients and P < 0.01 for each of the three groups of patients); the median UNCRs (and interquartile ranges) were 187 (135-231), 187 (165- 277), 218 (164-517) and 134 (97-152) mu mol/mol for PT, RR, SP patient s and controls, respectively. Similarly, patients had a greater median proportion of days with a UNCR above normal (P < 0.001 for all patien ts and P < 0.01 for each group); the median percentages (and interquar tile ranges) were 16 (6-62), 28 (21-36), 49 (14-86) and 0 (0-6)% for P P, RR, SP patients and controls, respectively. They also had a greater number of peaks in their serial UNCR measurements than controls (P < 0.001 for all patients and P < 0.01 for each group); the means+/-SD pe aks/subject/month were: 2.1+/-1.8; 3.0+/-1.7; 3.3+/-2.3 and 0.2+/-0.6 for PP, RR, SP patients and controls, respectively Nine relapses occur red in nine patients during the study and all were associated with inc reased neopterin excretion, which tended to be greater than that on da ys not associated with a relapse. Three of the nine relapses were prec eded by an upper respiratory tract infection. In eight out of 13 patie nts who had infections during the study, increased neopterin excretion was noted for periods of up to 6 weeks post-infection, significantly longer than that which occurred after infections in controls. This con firms infection as a potent inducer of symptomatic and asymptomatic di sease activity in mutiple sclerosis, and provides further support of a pivotal role for IFN-gamma in the pathogenesis of mutiple sclerosis. Urinary neopterin excretion is increased in patients with both progres sive and relapsing mutiple sclerosis, and therefore has potential as a surrogate marker of the inflammatory component of mutiple sclerosis d isease activity.