Alteration of cytokine production and augmented SLAM-expressing lymphocytes in acute multiple sclerosis

Antigen-stimulated interleukin-2 production and mitogen-stimulated type 1 and type 2 cytokine production by peripheral blood mononuclear cells, as well as expression of Th 1 and Th 2 -associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and serum concentration of soluble APO-1/Fas (sAPO-1/Fas) were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that: 1) antigen-stimulated IL-2 production is reduced in MS patients compared to HC; 2) mitogen-stimulated type 1 cytokine production is increased and IL-10 production is reduced in MS patient compared to HC, and in AMS compared to SMS; 3) whereas the production of the metabolically-active p70 heterodimers is comparable in SMS, AMS, and HC, the production of the p70 heterodimer + the p40 chains (total IL-12) is increased in SMS compared to AMS and HC; 4) CD4+, CD4+SLAM+, and CD4+/CD7+ lymphocytes (preferentially type 1 cytokines-producing lymphocytes) are increased in MS compared to HC; 5) B7-2 as well as Fas+ expressing monocytes are augmented in MS compared to HC, and serum sAPO-1/Fas is augmented in AMS compared to SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS, and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are overrepresented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.