INHIBITION OF LYMPHOCYTE BLASTOGENIC RESPONSE IN HEALTHY DONORS TREATED WITH RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF) - POSSIBLE ROLE OF LACTOFERRIN AND INTERLEUKIN-1 RECEPTOR ANTAGONIST

The effects of rhG-CSF on lymphocyte blastogenesis were evaluated in s ix healthy donors, submitted to progenitor cell mobilization for allog eneic transplantation. Neutrophil, monocyte and lymphocyte count incre ased 6.7-fold, 5.3-fold and 2.0-fold on day +4 of rhG-CSF as compared with baseline. The DNA stimulation index (DNA SI) of 72 h phytohemaggl utinin (PHA)-treated cultures decreased from 20% (15-35.5) prior to rh G-CSF to 6.7% (1.5-11.9; P = 0.0026), 8% (4-12; P = 0.0091) and 15% (9 -22; P = 0.0091) on days +2, +4 and +6; similarily, reactivity to conc anavalin A decreased from 18% (12-20) to 1.8% (0.5-7; P < 0.01), 3% (2 -8; P < 0.01) and 5% (2-11; P = 0.009). No changes of lymphocyte respo nse to pokeweed mitogen were observed. DNA SI of PHA-treated cultures inversely correlated with neutrophil and monocyte count. IL-1 receptor antagonist (IL-1ra) and lactoferrin (Lf) plasma levels sharply increa sed and correlated with neutrophil and monocyte count. IL-10 increased five-fold on day +2, returned to pretreatment values thereafter and d id not show any correlation with DNA SI, suggesting that it was not re sponsible for the observed phenomena. Interestingly; DNA SI of PHA-tre ated cultures inversely correlated with IL-1ra and Lf levels. CD3(+) a nd CD19(+) lymphocyte activation status, ie CD23, CD25, CD30 and HLA-D R coexpression, was not affected by rhG-CSF administration. Pharmacolo gical doses of rhG-CSF in healthy donors inhibit lymphocyte blastogene sis via an increased production and/or release of immunoregulatory sol uble mediators, ie IL-1ra and Lf, by primed neutrophils and monocytes.