Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions

Twenty-four heal thy male volunteers received either placebo or 75, 150, or 300 mu g filgrastim (recombinant methionyl human granulocyte colony-stimul ating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-alpha), in terleukin-12 (IL-12), and interferon gamma (IFN-gamma) release by whole blo od in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added i n vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-gamma and TNF-alpha release, suggesting that the anti-inflamm atory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphoc yte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgr astim induced doubling of all T-cell populations by day 8. Filgrastim decre ased proinflammatory cytokine production and lymphocyte proliferation ex vi vo throughout prolonged treatment at all doses. This indicates that endogen ous granulocyte colony-stimulating factor may counterregulate the inflammat ory cytokine cascade and implies a potential indication for filgrastim in c hronic inflammatory conditions.