Acute Inflammatory Response to Endotoxin in Mice and Humans

American Society for Microbiology - Tập 12 Số 1 - Trang 60-67 - 2005
Shannon Copeland1, H. Shaw Warren2, Stephen F. Lowry3, Steve E. Calvano3, Daniel G. Remick4
1Department of Pathology, University of Michigan, M2210 Medical Sciences Bldg. I, 1301 Catherine Rd., Ann Arbor, MI 48109-0602, USA.
2Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
3Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey
4Department of Pathology, University of Michigan, Ann Arbor, Michigan

Tóm tắt

ABSTRACT

Endotoxin injection has been widely used to study the acute inflammatory response. In this study, we directly compared the inflammatory responses to endotoxin in mice and humans.Escherichia colitype O113 endotoxin was prepared under identical conditions, verified to be of equal biological potency, and used for both mice and humans. The dose of endotoxin needed to induce an interleukin-6 (IL-6) concentration in plasma of ∼1,000 pg/ml 2 h after injection was 2 ng/kg of body weight in humans and 500 ng/kg in mice. Healthy adult volunteers were injected intravenously with endotoxin, and male C57BL/6 mice (n= 4 to 12) were injected intraperitoneally with endotoxin. Physiological, hematological, and cytokine responses were determined. Endotoxin induced a rapid physiological response in humans (fever, tachycardia, and slight hypotension) but not in mice. Both mice and humans exhibited lymphopenia with a nadir at 4 h and recovery by 24 h. The levels of tumor necrosis factor (TNF) and IL-6 in plasma peaked at 2 h and returned to baseline levels by 4 to 6 h. IL-1 receptor antagonist RA and TNF soluble receptor I were upregulated in both mice and humans but were upregulated more strongly in humans. Mice produced greater levels of CXC chemokines, and both mice and humans exhibited peak production at 2 h. These studies demonstrate that although differences exist and a higher endotoxin challenge is necessary in mice, there are several similarities in the inflammatory response to endotoxin in mice and humans.

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American Society for Microbiology

Tập 12 Số 1

60-67

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