Effect of isotretinoin therapy on natural killer cell activity in patients with xeroderma pigmentosum.
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by sun sensitivity, defective DNA repair, markedly increased susceptibility to skin cancer, and a variety of immunological defects, including defective natural killer (NK) cell activity. Retinoid therapy has been demonstrated to protect effectively against the development of skin cancers in patients with XP, although its mechanism of action is unknown. We describe a series of eight XP patients, six of whom were given oral isotretinoin. The NK cell activity was not affected by low-dose isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK cell function, at the same time as producing a reduction in the frequency of development of skin cancers. Retinoid therapy may have a skin cancer preventing effect by enhancing other immune effector mechanisms or via epithelial cell differentiation.
Anolik
J H
JH
Department of Dermatology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, USA.
Di Giovanna
J J
JJ
Gaspari
A A
AA
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015474:Isotretinoin / Q000627:therapeutic use*; D007641:Keratolytic Agents / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014983:Xeroderma Pigmentosum / Q000188:drug therapy* / Q000276:immunology
D007376:Interleukin-2; D007641:Keratolytic Agents; D014409:Tumor Necrosis Factor-alpha; D015474:Isotretinoin