SUMMARYNeutrophils accumulate in the acute blood vessel lesions of patients with autoimmune systemic vasculitis. They have been shown previously to produce the cytokine IL-1¯in response to stimulation with TNF. This study demonstrates that neutrophils can be stimulated by anti-neutrophil cytoplasmic antibodies (ANCA), which are present in patients with systemic vasculitis, to express mRNA and protein for IL-1¯. Both human ANCA and MoAbs to a variety of autoantigens recognized by ANCA, including proteinase 3, myeloperoxidase, bactericidal/permeability increasing protein and elastase, are effective. This response can be inhibited by actinomycin and cycloheximide, suggesting a requirement for de novo protein synthesis. IL-1¯production can be inhibited by pooled human intravenous immunoglobulins but not by FK506 or cyclosporin A. These data suggest that ANCA in patients with active vasculitis may stimulate neutrophils to produce cytokines. It is hypothesized that cytokine production from neutrophils that accumulate in significant numbers in vasculitic lesions contribute to and augment the local inflammatory response by the activation of vascular endothelial cells and infiltrating leucocytes.
These data are consistent with the hvpothesis that programmed alterations to renal structure are reflected in progressive deterioration HJ NEWBERY', N FISHER^, M PIRMOHAMED", NR
KITTERINGHAM' IT GILMORE', D ADAMS3 and BK PARK'Evidence from twin, longitudinal and cross-sectional studies suggests that alcoholic liver disease is multifactorial in aetiology, with genetic and environmental factors interacting in its pathogenesis. A role for TNFu in this process is supported both by observations of raised levels of TNFU, correlating with disease severity, and the association of promoter region polymorphisms with the disease. Furthermore,
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.