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 six healthy donors, submitted to progenitor cell mobilization for allogeneic transplantation. Neutrophil, monocyte and lymphocyte count increased 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 phytohemagglutinin (PHA)-treated cultures decreased from 20% (15-35.5) prior to rhG-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; similarly, reactivity to concanavalin 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 response 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 increased and correlated with neutrophil and monocyte count. IL-10 increased five-fold on day +2, returned to pretreatment values thereafter and did not show any correlation with DNA SI, suggesting that it was not responsible for the observed phenomena. Interestingly, DNA SI of PHA-treated cultures inversely correlated with IL-1ra and Lf levels. CD3+ and CD19+ lymphocyte activation status, ie CD23, CD25, CD30 and HLA-DR coexpression, was not affected by rhG-CSF administration. Pharmacological doses of rhG-CSF in healthy donors inhibit lymphocyte blastogenesis via an increased production and/or release of immunoregulatory soluble mediators, ie IL-1ra and Lf, by primed neutrophils and monocytes.
Rutella
S
S
Center for the Flow Cytometric Study of Blood Cells and Department of Hematology, Catholic University, Rome, Italy.
Rumi
C
C
Testa
U
U
Sica
S
S
Teofili
L
L
Martucci
R
R
Peschle
C
C
Leone
G
G
D000328:Adult; D015703:Antigens, CD / Q000097:blood / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000187:drug effects / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000097:blood / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007781:Lactoferrin / Q000097:blood / Q000187:drug effects / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000097:blood / Q000187:drug effects / Q000502:physiology
D015703:Antigens, CD; D006684:HLA-DR Antigens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D007781:Lactoferrin