Th 1 cytokine production by peripheral blood mononuclear cells in X-linkedadrenoleukodystrophy

Cerebral adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) are the two most frequent clinical phenotypes of the same genetic defect leading t o the accumulation of very long chain fatty acids (VLCFA). Previous studies have suggested that inflammatory cytokines may play a role in the cerebral demyelination and in phenotype expression of the disease. We analyzed cyto kine production by stimulated peripheral blood mononuclear cells (PBMC) fro m 17 patients (four asymptomatic subjects, eight AMN and five ALD). Our res ults show that lipopolysaccarides (LPS) stimulated PBMC from both symptomat ic and asymptomatic patients have an increased production of IL-12 and TNF alpha compared to controls, while after phitoemoagglutinin (PHA) stimulatio n we observed a decreased production of IL-6 and IL-10. These data indicate that, following an immunological stimulus, PBMC from patients have an incr eased production of cytokines typical of a Th1 cell response which is able to promote the inflammatory process. This characteristic profile of cytokin e production could be related to the biochemical defect and could have a ro le in central nervous system (CNS) pathogenesis. (C) 2001 Elsevier Science BN: All rights reserved.