Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis

It has been shown that proinflammatory and antiinflammatory cytokines corre late with disease activity in multiple sclerosis (MS). To establish whether such correlations depend on the disease stage, we assessed in a longitudin al fashion the expression of interleukin (IL)-12 (p40 and p35), tumor necro sis factor-alpha, interferon-gamma, and IL-10 mRNA by competitive polymeras e chain reaction in unstimulated peripheral blood mononuclear cells of rela psing-remitting (RR) and secondary progressive (SP) MS patients, in relatio n to monthly clinical and magnetic resonance imaging monitoring, MS patient s had increased levels of IL-12p40 and decreased levels of IL-10 mRNA compa red with controls; this difference was most pronounced in SP patients. Both RR and SP patients had increased levels of IL-12p40 mRNA compared with con trols during the development of active lesions. Moreover, in RR MS an incre ase was found before relapse. IL-12p35 mRNA was decreased in both groups, a nd in relation to disease activity it showed a pattern different from IL-12 p40 mRNA. In RR MS, IL-10 mRNA was low 4 weeks before magnetic resonance im aging activity and 6 weeks before relapse; a significant increase to normal levels was noted when active lesions became apparent. In contrast, SP pati ents showed low IL-10 mRNA levels constitutively, suggesting that IL-10 pla ys an important role in the control of disease progression.