EFFECTS OF GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) TREATMENT ONGRANULOCYTE FUNCTION AND RECEPTOR EXPRESSION IN PATIENTS WITH VENTILATOR-DEPENDENT PNEUMONIA

Considerable experimental evidence in animals suggests that treatment with G-CSF may have a beneficial effect in the management of severe in fections in non-neutropenic hosts. This beneficial effect is attribute d to an enhancement of granulopoiesis and neutrophil function, the lat ter possibly involving up-regulation of receptors on neutrophils that are involved in antibody-mediated cytotoxicity and killing of microorg anisms. We compared neutrophil function and phenotype in blood and bro nchoalveolar lavage fluid (BALF) of 10 patients with severe ventilator -dependent pneumonia, at baseline and following initiation of G-CSF tr eatment as adjunct to standard therapy. G-CSF treatment was associated with three-fold increased blood neutrophil counts at day 3 of treatme nt compared with baseline counts. Mean serum G-CSF concentration incre ased from 313 to 2007 pg/ml. After correction for lavage dilution effe cts, BALF G-CSF levels did not differ significantly from baseline, nor did neutrophil receptor expression (Fc gamma RI, Fc gamma RII, Fc gam ma RIII, CR3, and L-selectin) or indicators of neutrophil function suc h as respiratory burst activity, phagocytosis and killing of Candida a lbicans in BALF or blood. The mortality in this group of patients was 30% and compared favourably to the APACHE II-derived predicted mortali ty of 60%. We conclude that the possible therapeutic benefit of G-CSF administration in the early phase of severe bacterial pneumonia is not readily explained by its effect on baseline indicators of neutrophil function or receptor expression.