THE EFFECTS OF TREATMENT WITH PIXY321 (GM-CSF IL-3 FUSION PROTEIN) ONHUMAN POLYMORPHONUCLEAR LEUKOCYTE FUNCTION/

During a phase I trial of the genetically engineered hematopoietic gro wth factor PIXY321 (granulocyte-macrophage colony-stimulating factor/i nterleukin-3 [IL-3] fusion protein), we examined the effects of PIXY32 1 treatment on human polymorphonuclear leukocyte (PMN) locomotive, res piratory burst, and phagocytic responses. PIXY321 treatment was associ ated with transient suppression of both unstimulated locomotion and ch emotaxis responses to multiple stimuli, as well as significant transie nt enhancement of formyl peptide-stimulated H2O2, production. No effec ts on opsonic phagocytosis of Staphylococcus aureus were observed. In vitro exposure of control PMN to PIXY321 resulted in suppression of un stimulated locomotion/chemotaxis and enhancement of formyl peptide-sti mulated H2O2 production but had no effects on phagocytosis. When patie nt cells were exposed in vitro to PIXY321 during treatment, suppressio n of chemotaxis and enhancement of H2O2 production were observed befor e PIXY321 treatment, but these effects diminished during treatment. Th e in vivo and in vitro exposure effects of PIXY321 treatment on PMN fu nction are similar to those of the parent molecule, granulocyte-macrop hage colony-stimulating factor (GM-CSF).