BACILLUS-CALMETTE-GUERIN ENHANCEMENT OF COLONY-STIMULATING ACTIVITY AND MYELOID COLONY FORMATION FOLLOWING ADMINISTRATION OF CYCLOPHOSPHAMIDE

Abstract

Pretreatment of mice with BCG [an immunologic drug used to treat human tumors] enhances recovery of the peripheral granulocyte count from cyclophosphamide (CTX)[an antitumor agent]-induced leukopenia. In vitro bone marrow culture was used to assess the effect of BCG pretreatment on serum levels of myeloid colony-stimulating activity and on regeneration of bone marrow myeloid colony-forming units (CFU-c) following CTX. C57BL/6 mice received either BCG or 0.9% NaCl solution i.p. 8 days prior to the administration of CTX (300 mg/kg i.p.). Following CTX, peak serum levels of myeloid colony-stimulating activity were strikingly higher in the BCG-pretreated mice [1320 .+-. 30 (S.E.) units] than in the 0.9% NaCl solution-pretreated mice (764 .+-. 37 units). BCG pretreatment also resulted in higher numbers of marrow CFU-c during recovery from CTX (e.g., 43.9 .+-. 1.8 vs. 20.0 .+-. 0.9 myeloid colonies/105 marrow cells, Day 3 post-CTX). However, neither the rate of decline nor the absolute nadir of CFU-c, nor CFU-c cell cycle characteristics were affected by the pretreatment. The initial effect of i.p. BCG pretreatment on recovery from CTX-induced granulocytopenia is an augmentation of serum myeloid colony-stimulating activity which precedes the enhanced regeneration of CFU-c and the accelerated recovery of the peripheral granulocyte count.