SULFATIDE AND ITS PRECURSOR GALACTOSYLCERAMIDE INFLUENCE THE PRODUCTION OF CYTOKINES IN HUMAN MONONUCLEAR-CELLS

Sulphatide is expressed in the central and peripheral neural system, i n islets of Langerhans, and in tissues affected by late diabetic compl ications. Autoantibodies to sulphatide are present in patients with in sulin-dependent diabetes and the Guillain-Ban-C syndrome. Cytokines in fluence these disease processes, and we therefore studied whether sulp hatide and its precursor galactosylceramide (gal-cer) influence the in vitro production of cytokines by blood monunuclear cells (MNC) origin ating from 15 healthy persons. Using lipopolysaccharide (LPS)-stimulat ed cells, sulphatide increased the IL-2. production (163 +/- 17% of co ntrols without sulphatide. p = 0.02), and gal-cer increased the IL-1 a lpha production (145 +/- 13%, p = 0.006), whereas neither gal-cer nor sulphatide had an effect on the production of IL-6, IL-10 or TNF alpha . When stimulating cells with phytohaemagglutinin (PHA), sulphatide de creased the production of IL-6 (88 +/- 5%, p = 0.009), IL-10 (66 +/- 3 %, p = 0.000003), and TNF alpha (75 +/- 9%: p = 0.02). Gal-cer, howeve r. increased the production of IL-6 (188 +/- 13%, p = 0.000006), and d ecreased the production of TNF beta (80 +/- 6%, p = 0.007). Neither ga l-cer nor sulphatide had an effect on the production of IL-2 or IFN ga mma from PHA-stimulated cells. Northern blot analysis using an IL-6 pr obe similarly showed an increased amount of IL-6 mRNA after gal-cer in cubation (range 469%-150%, n = 3) of PHA-stimulated control. Thus, sul phatide and gal-cer influence the production of several cytokines thou ght to be involved in immunoinflammatory disease processes.