Pretreatment with granulocyte-colony stimulating factor decreases lipopolysaccharide-induced interferon-γ production in mice in association with the production of interleukin-18

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2004-02, Vol.25 (3), p.119-126
• Main Authors: Shaklee, Christine L., Guo, Jane, Faggioni, Raffaella, Fantuzzi, Giamila, Senaldi, Giorgio
• Format: Article
• Language: English
• Subjects: Animals; Cytokines - blood; Cytokines - genetics; Cytokines - metabolism; Female; G-CSF; Gene Expression - drug effects; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte Colony-Stimulating Factor - physiology; IFN-γ; IL-18; Interferon-gamma - blood; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin-10 - blood; Interleukin-10 - genetics; Interleukin-12 - blood; Interleukin-12 - genetics; Interleukin-12 Subunit p40; Interleukin-18 - analysis; Interleukin-18 - genetics; Interleukin-18 - metabolism; Interleukin-6 - blood; Interleukin-6 - genetics; Leukocyte Count; Lipopolysaccharides - pharmacology; Liver - chemistry; Liver - drug effects; Liver - metabolism; LPS; Mice; Mice, Inbred BALB C; Neutrophils; Protein Subunits - blood; Protein Subunits - genetics; Recombinant Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Spleen - chemistry; Spleen - drug effects; Spleen - metabolism; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2003.10.007

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-γ (IFN-γ) and higher levels of interleukin (IL)-6 and IL-10 than controls. G-CSF-pretreated mice also had lower mRNA levels of IFN-γ 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-γ and spleen IL-18 than controls. G-CSF pretreatment alters the expression of LPS-induced cytokines with a decrease in pro-inflammatory IFN-γ 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-γ.