Sulphatide and its precursor galactosylceramide influence the production of cytokines in human mononuclear cells.

Abstract

Sulphatide is expressed in the central and peripheral neural system, in islets of Langerhans, and in tissues affected by late diabetic complications. Autoantibodies to sulphatide are present in patients with insulin-dependent diabetes and the Guillain-Barré syndrome. Cytokines influence these disease processes, and we therefore studied whether sulphatide and its precursor galactosylceramide (gal-cer) influence the in vitro production of cytokines by blood mononuclear cells (MNC) originating from 15 healthy persons. Using lipopolysaccharide (LPS)-stimulated cells, sulphatide increased the IL-2 production (163 +/- 17% of controls without sulphatide, p = 0.02), and gal-cer increased the IL-1 alpha 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 decreased 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, however, increased the production of IL-6 (188 +/- 13% p = 0.000006), and decreased the production of TNF beta (80 +/- 6%, p = 0.007). Neither gal-cer nor sulphatide had an effect on the production of IL-2 or IFN gamma from PHA-stimulated cells. Northern blot analysis using an IL-6 probe similarly showed an increased amount of IL-6 mRNA after gal-cer incubation (range 469%-150%, n = 3) of PHA-stimulated control. Thus, sulphatide and gal-cer influence the production of several cytokines thought to be involved in immunoinflammatory disease processes.