EFFECT OF IFN-ALPHA ON NORMAL HUMAN HEMATOPOIESIS - AN IMMUNOHISTOCHEMICAL AND MORPHOMETRIC STUDY ON TREPHINE BIOPSY SPECIMENS

To elucidate the effects of interferon-alpha (IFN-alpha) on normal hum an bone marrow in vivo, an immunomorphometric study was performed usin g trephine biopsy specimens without hematopoietic pathology. Samples w ere derived from patients with mycosis fungoides but no marrow involve ment, who were undergoing low-dose IFN-alpha treatment. Parameters inc luded density of reticulin (argyrophilic) fibers, CD61(+) megakaryocyt es, PG-M-1(+) macrophages, the GSA-I lectin-expressing (activated) mac rophage subpopulation, proliferative activity (PCNA staining), and apo ptosis, Following IFN-alpha therapy (3 x 3 x 10(6) U/week between 6 an d 21 months), morphometric evaluation of sequential bone marrow examin ations revealed a significent increase in the number of megakaryocytes and the amount of reticulin fibers. Additionally, there was an overal l decrease in PCNA(+) cells, accompanied by a reduction in the inciden ce of apoptotic bodies. On the other hand, total number of macrophages and their activated subfraction remained unchanged. Opposed to in vit ro findings, a fibrogenetic capacity of IFN-alpha associated with mega karyocyte growth was detectable. Moreover, contrasting with effects of IFN-alpha treatment in chronic myelogenous leukemia, the incidence of apoptosis was significantly reduced. This feature was assumed to cont ribute to a maintenance of steady-state hematopoiesis expressed by a n onaltered bone marrow cellularity in our specimens.