Excessive production of tumour necrosis factor alpha by peripheral blood mononuclear cells in X-linked...

Previous studies have suggested that cytokine production may play a role in the cerebral demyelination and phenotypical variations of X-linked adrenoleukodystrophy (ALD). At initial evaluation, the serum titre of tumour necrosis factor alpha (TNFalpha) but not interleukin IL-1alpha, IL-1beta, IL-6, IL-4 and interferon INF-gamma of 12 ALD patients with cerebral demyelination, was higher than that of controls and of six ALD patients without cerebral demyelination. However, TNFalpha was not detected in the cerebrospinal fluid of the same patients with cerebral demyelination. In a serial study of 15 patients over 2-5 years, the level of serum TNFalpha paralleled the progression of demyelination. Peripheral blood mononuclear cells from 15 symptomatic ALD patients, irrespective of their clinical phenotype, produced higher levels of TNFalpha than controls after in vitro stimulation by lipopolysaccharide. The production of other cytokines was normal. Abnormal production of TNFalpha was observed in two of six asymptomatic ALD patients but was absent in both of two bone marrow transplanted ALD patients. These data suggest that monocytes of ALD patients have an intrinsic alteration in the regulatory pathway of TNFalpha production.