CYTOKINE EXPRESSION BY INFLAMMATORY NEUTROPHILS

Bloodstream neutrophils do not express mRNA for interleukin-1beta (IL- 1beta), but transcripts for this cytokine are rapidly induced followin g exposure to recombinant granulocyte-macrophage colony-stimulating fa ctor (rGM-CSF) in vitro. Levels of IL-1beta mRNA reach maximal values 1 h after exposure to TGM-CSF and then decline to near basal levels by 4 h. Similarly, rGM-CSF treatment of blood neutrophils in vitro induc ed increases in levels of mRNA for IL-6 and tumour necrosis factor-alp ha (TNF-alpha). RNA extracted from neutrophils isolated from the synov ial fluid of patients with rheumatoid arthritis expressed low, but sig nificant levels of IL-1beta mRNA that were between 0.5 and 3% of the l evels that could be maximally induced by rGM-CSF treatment of blood ne utrophils. However, transcripts for TNF-alpha and IL-6 were not detect ed in these synovial fluid neutrophils. mRNA for transforming growth f actor-beta (TGF-beta) was constitutivety expressed in blood and synovi al fluid neutrophils and transcripts for this cytokine were not altere d by rGM-CSF exposure. Because of the transient nature of IL-1beta exp ression by activated neutrophils, we propose that the low levels of ex pression of mRNA for this cytokine in the synovial fluid neutrophils r epresents expression by a small, perhaps newly-recruited and activated , sub-population of cells. IL-1beta expression by this sub-population may thus contribute to the pathogenesis of rheumatoid disease.