title: IL-6 plays an essential role in neutrophilia under inflammation.
abstract: In the present study, we explored the involvement of interleukin-6 (IL-6) in neutrophilia under inflammatory conditions. The neutrophil count in the peripheral blood was high in arthritic monkeys, and anti-IL-6 receptor antibody reduced neutrophil counts to normal levels. IL-6 injection into normal monkeys significantly increased neutrophil counts in the blood 3h after injection. The expression of cluster of differentiation (CD) 162 on circulating neutrophils was reduced by IL-6 injection. IL-6 treatment in vitro did not affect CD162 expression on neutrophils from human blood. In IL-6-treated monkeys, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in plasma were clearly elevated. IL-8 and GM-CSF treatment in vitro reduced cell-surface CD162 expression on human neutrophils, and moreover, increased soluble CD162 expression in the cell supernatant. The addition of IL-6 into human whole peripheral blood induced IL-8 production and reduced CD162 expression on neutrophils. Furthermore, IL-8 and GM-CSF augmented mRNA expression of a disintegrin and metalloprotease like domain 10 (ADAM10) in neutrophils. Knock-down of ADAM10 by siRNA in neutrophil-like HL-60 cells partially reversed the expression of CD162 reduced by GM-CSF and IL-8 on HL-60 cells. In conclusion, IL-6 induced neutrophilia and reduced CD162 expression on neutrophils in inflammation.
authors.affiliation: Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Hashizume
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000097:blood; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood; D005434:Flow Cytometry / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood; D008252:Macaca fascicularis; D008562:Membrane Glycoproteins / Q000097:blood*; D008565:Membrane Proteins / Q000097:blood; D009504:Neutrophils / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C084882:P-selectin ligand protein; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human