Changes in HLA-DR expression, cytokine production and coagulation following endotoxin infusion in healthy human volunteers

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• 作者：Timothy G.K. Mant ; Svetlana Borozdenkova ; Daniel B.A. Bradford ; Elizabeth Allen ; Dipti M. Amin ; Roger D. Toothaker ; Robert W.M. Collins ; Roseanna E.G. Hargreaves ; Stipo Jurcevic
• 关键词：Endotoxin ; HLA-DR expression ; Cytokines ; Coagulation
• 刊名：International Immunopharmacology
• 出版年：2008
• 出版时间：May 2008
• 年：2008
• 卷：8
• 期：5
• 页码：701-707
• 全文大小：587 K

文摘

The infusion of a low dose of endotoxin into healthy subjects triggers a complex inflammatory response but the intricacies of which, despite extensive research, are still being unraveled. Nine healthy male volunteers received a dose of 30 Units endotoxin/kg bodyweight as an intravenous bolus. Following endotoxin infusion the concentration of TNF-alpha in their serum rapidly increased within 30 min, peaked after 1–2 h and returned to baseline by 4 h. This corresponded to a similarly rapid increase in anti-inflammatory soluble TNF receptor (sTNFR) levels, which remained elevated for up to 48 h. Increased levels of other cytokines were measured, including IL-6, IL-8, G-CSF, IL-1ra and IL-10. However, these cytokines lagged behind that of TNF-alpha and remained elevated for up to 8 h. Endotoxin injection resulted in complex changes in HLA-DR expression, a marker of monocyte activation state. Initially, following a lag of 2–4 h, HLA-DR expression decreased with a nadir at 8 h, followed by an increase in expression above baseline at 22 h. HLA-DR levels returned to baseline 48 h post-endotoxin challenge. This was in contrast to endotoxin-induced changes in white blood cell (WBC) numbers, which dropped rapidly (at 2–3 h) while HLA-DR levels were stable and then peaked during the nadir in HLA-DR expression (8 h). Furthermore, endotoxin injection caused activation of both fibrinolytic and coagulation pathways. Thus, endotoxin infusion results in complex changes in HLA-DR expression, production of pro- and anti-inflammatory cytokines and activation of coagulation.