Efficacy of ascorbic acid in Chediak-Higashi syndrome (CHS): studies in humans and mice.

The efficacy of ascorbic acid therapy in Chediak-Higashi syndrome (CHS) was assessed in two humans and in the mouse model of this disease. Ascorbic acid (6 g/day) was given for 8 mo to two brothers (26 and 27 yr old) with CHS. The therapy had no effect on the clinical course of these patients and no change in their complete blood count or abnormal leukocyte morphology (giant lysosomes). In addition, the leukocyte dysfunction seen in this disease was not improved by ascorbic acid; skin window responses, chemotaxis, and bactericidal activity remained abnormal and there was no change in lymphocyte function. No abnormality of leukocyte cAMP or cGMP was seen in our patients, and no changes in basal cyclic nucleotides occurred during ascorbic acid therapy. In other studies high doses of intraperitoneal ascorbic acid (20 mg/mouse) prolonged the survival of CHS mice from lethal infection with Candida albicans, although the survival of CHS treated mice was not as good as that of saline-treated controls. Ascorbic acid also improved polymorphonuclear leukocyte chemotaxis and bactericidal activity for Staphylococcus aureus. Despite the improved function there was no change in the morphology of CHS mouse leukocytes after ascorbic acid therapy. In addition, we found no abnormality of basal leukocyte cyclic nucleotide levels and no change in basal cyclic nucleotides after ascorbic acid therapy. These data indicate that although ascorbic acid may have a beneficial effect in mice with CHS, patients with CHS may not respond in a similar manner.