Circadian Rhythms and Differences in Epidermal and in Dermal Cell Proliferation in Uninvolved and Involved Psoriatic Skin In Vivo

Abstract

Using in vivo DNA labeling procedures, the present study makes a detailed comparative analysis of circadian rhythms in labeling indexes (Is), in mitotic indexes (Im), and in Is/Im ratios in uninvolved and in involved psoriatic epidermis in vivo (12 patients, studied at 6-hr intervals over a 24-hr period). We also provide comparable data on the rates of epidermal DNA synthesis and on the proliferative activity of dermal infiltrate cells. There are no circadian-diurnal variations in epidermal or in dermal infiltrate cell proliferation in either inactive (uninvolved) or in active (involved) lesions of psoriatic skin. The rates of epidermal DNA synthesis were lower at 9 AM and 3 PM; higher at 9 PM and 3 AM in both uninvolved and involved epidermis. The following cell kinetic information was derived from 78 biopsy samples-from epidermal mitotic and labeled nuclei counts in approximately 100 mm unit lengths of epidermis per biopsy. DNA labeling indexes, 6.1 vs. 21.2%; mitotic indexes, 0.13 vs. 0.43%; and Is/Im ratios, 152/1 vs 70/1 in uninvolved vs. involved psoriatic epidermis in vivo. There was an overall 20% decrease in the rate of cycling epidermal cell DNA synthesis involved epidermis; and 5-fold increase in the overall proliferative activity of dermal infiltrate cells in involved psoriatic skin. These results are discussed in relation to the clinical use of circadian rhythms for the "chronotherapy" of proliferative diseases in man, in relation to cell cycle aspects of psoriasis and psoriatic epidermal responses to therapy, and in relation to cell proliferation in human epidermis in vivo.