PATHOGENESIS OF FEVER IN HUMANS

人类发烧的发病机制

• 批准号: 2707851
• 负责人: Charles anthony Dinarello
• 金额: $ 34.04万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2707851
• 关键词: PATHOGENESIS; FEVER; HUMANS

This proposal concerns interleukin-1 (IL-1) as a key mediator of host responses to microbial invasion, inflammation, immunological reaction and injury. IL-1 is one of the first and most prominent molecular synthesized following the onset of infection or injury. Many of IL-1's effects are involved with pathological processes, and the host has mechanisms by which synthesis, processing, transport and activities of IL-1 are regulated. This proposal studies these various mechanisms. The experiments are designed to explore IL-1 production from human blood monocytes. Up to 5% of the total polyadenylated RNA codes for IL-1-beta in monocytes after stimulation. Mechanisms control the translation of this RNA into IL-1 protein whereas other mechanisms seem to control processing of the primary translation product into biologically active IL-1. Transcription, translation and processing of IL-1 are different in blood monocytes than in cultured cells lines. Therefore, these experiments are focused on each of the steps of IL-1 production in circulating human blood cells in health, in disease and under the influence of various disease modifying substances. special methods will be employed that prevent the transcription of Il-1 in monocytes due to adherence to surfaces. Two newly developed radioimmunoassays for IL-1-beta and Il-1- alpha will be used in a large study to establish what constitutes "normal" Il-1 production. Immunoprecipitation and immunofluorescence using specific, non-cross reacting antibodies will be used to detect the sizes and cellular localization of IL-1. The specific biological activities of Il-1 differ with the molecular size and hence studies on the structure-function relationship of IL-1 are proposed in order to identify a putative active site(s). The evaluation of synthetic peptides will be performed and correlated with naturally occurring fragments of monocyte Il-1. An animal model of hemodynamic shock using toxic shock syndrome toxin is to be used to evaluate the systemic effects of Il-1, its fragments and substances that inhibit its biological activities. Two clinical models will be used to study Il-1 production in human subjects: the effect of supplemental fish oil diet and hemodialysis. These studies complement the basic investigations on the molecular control of IL-1 production. Finally, these studies examine the production and activity of IL-1 in models of endogenous amplification and inhibition.

这一建议关注白细胞介素-1 （IL-1）作为一个关键的调节因子

项目成果

Interleukin-37 Inhibits Colon Carcinogensis During Chronic Colitis

• DOI: 10.3389/fimmu.2019.02632
• 发表时间: 2019-11
• 期刊: Frontiers in Immunology
• 影响因子: 7.3
• 作者: S. Mountford;A. Ringleb;R. Schwaiger;D. Mayr;S. Kobold;C. Dinarello;P. Bufler