Thymopentin in SÉzary Syndrome: Clinical and Immunological Effects

Abstract

Thymopentin (TP-5) is a synthetic pentapeptide, Arg-Lys-Asp-Val-Tyr, corresponding to the active site of the linear 48-amino acid human hormone, thymopoietin. T helper cell immunostimulation by TP-5 has been demonstrated in a number of animal models and in man. TP-5 restores defective IL-2 levels in aged and thymectomized mice. Increases in cytotox-ic/suppressor lymphocytes and in vivo enhancement of NK cell activity have been reported to be induced by this pentapeptide. In this paper, the results of TP-5 treatment in 21 patients with Sézary syndrome (SS), including clinical, immunologic and histologic effects on skin clearing, are examinated. No in vitro effect of TP-5, alone, at any concentration, could be demonstrated in Sézary cells; however, the combination of TP-5 and phytohemagglutin (PHA) induced an increment in proliferative response which was only seen in cells from the Sézary syndrome patients. Eight complete remissions and eight partial remissions (76%) were obtained in 21 patients treated by intravenous injection with TP-5, 50 mg three times per week, for a median duration of 15 months of treatment (3-36 months). The response was accompanied by an increase in peripheral blood Sézary cell proliferative activity and an increase in the expression of CD8 and activation antigens, including CD25, and in CD16⁺CD56⁺ cells. By contrast, a significant decrease in CD25 and other activation antigens was found in the skin infiltrate. This reduction paralleled the loss of epidermotropism and the almost complete disappearance of the infiltrate in responsive cases. Circulating levels of soluble interleukin-2 receptor (sIL-2R) were determined before and during TP-5 treatment in 19 of the 21 patients. Pretreatment values were 900-2,000 U/ml in 4 patients and > 4,000 U/ml (range, 4,519–18,800 U/ml) in the remainder. A decrease was observed during TP-5 treatment in 13 of 19 patients, an increase in four and no change in two. In six of eight patients in whom a complete remission was obtained, sIL-2R levels returned to normal.