Cytokine expression by inflammatory neutrophils.
Bloodstream neutrophils do not express mRNA for interleukin-1 beta (IL-1 beta), but transcripts for this cytokine are rapidly induced following exposure to recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in vitro. Levels of IL-1 beta mRNA reach maximal values 1 h after exposure to rGM-CSF and then decline to near basal levels by 4 h. Similarly, rGM-CSF treatment of blood neutrophils in vitro induced increases in levels of mRNA for IL-6 and tumour necrosis factor-alpha (TNF-alpha). RNA extracted from neutrophils isolated from the synovial fluid of patients with rheumatoid arthritis expressed low, but significant levels of IL-1 beta mRNA that were between 0.5 and 3% of the levels that could be maximally induced by rGM-CSF treatment of blood neutrophils. However, transcripts for TNF-alpha and IL-6 were not detected in these synovial fluid neutrophils. mRNA for transforming growth factor-beta (TGF-beta) was constitutively expressed in blood and synovial fluid neutrophils and transcripts for this cytokine were not altered by rGM-CSF exposure. Because of the transient nature of IL-1 beta expression by activated neutrophils, we propose that the low levels of expression of mRNA for this cytokine in the synovial fluid neutrophils represents expression by a small, perhaps newly-recruited and activated, sub-population of cells. IL-1 beta expression by this sub-population may thus contribute to the pathogenesis of rheumatoid disease.
Quayle
J A
JA
Department of Biochemistry, University of Liverpool, UK.
Adams
S
S
Bucknall
R C
RC
Edwards
S W
SW
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013582:Synovial Fluid / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor