Pretreatment with granulocyte-colony stimulating factor decreases lipopolysaccharide-induced interferon-gamma production in mice in association with the production of interleukin-18.
We studied the effects of pretreatment with granulocyte-colony stimulating factor (G-CSF) on the production of pro- and anti-inflammatory cytokines induced by lipopolysaccharide (LPS). Mice received G-CSF or control saline once a day for 7 days or once at 1 h before the injection of LPS. Cytokines were measured by enzyme-linked immunosorbent assay or antibody-based electrochemiluminescence assay and cytokine mRNA was measured by RNAse protection assay. Mice pretreated with G-CSF for 7 days before LPS had lower serum levels of LPS-induced interferon-gamma (IFN-gamma) and higher levels of interleukin (IL)-6 and IL-10 than controls. G-CSF-pretreated mice also had lower mRNA levels of IFN-gamma and higher mRNA levels of IL-6 and IL-10 in the spleen and/or liver than controls. G-CSF-pretreated mice had serum levels of tumor necrosis factor, IL-12 p70 and IL-12 p40 similar to controls. G-CSF-pretreated mice had lower levels of spleen IL-18 than controls-serum IL-18 being undetectable in mice after LPS-and lower levels of IL-18 mRNA in the spleen. Mice pretreated with G-CSF 1 h before LPS had lower levels of serum IFN-gamma and spleen IL-18 than controls. G-CSF pretreatment alters the expression of LPS-induced cytokines with a decrease in pro-inflammatory IFN-gamma and an increase in anti-inflammatory IL-6 and IL-10. G-CSF decrease of IL-18 production may be a major mechanism explaining the effects of G-CSF on the production of IFN-gamma.
Shaklee
Christine L
CL
Amgen Inc., Thousand Oaks, CA 94555, USA.
Guo
Jane
J
Faggioni
Raffaella
R
Fantuzzi
Giamila
G
Senaldi
Giorgio
G
D000818:Animals; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology*; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D021122:Protein Subunits / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D013154:Spleen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D015850:Interleukin-6; D008070:Lipopolysaccharides; D021122:Protein Subunits; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D007371:Interferon-gamma