Interleukin-6 is a better marker of lethality than tumor necrosis factor in endotoxin treated mice.
We established a mouse model to differentiate between a lethal and non-lethal presentation of endotoxic shock. The model involved injecting different amounts of Escherichia coli LPS into C3H/HeN mice which had been 'primed' with BCG. We found that the mice receiving non-lethal and lethal doses of LPS could not be differentiated in terms of their physical symptoms for the first 8 h post-injection. Tumour necrosis factor (TNF) was detected at concentrations 2-9-fold greater in mice receiving lethal doses of LPS when compared with non-lethally injected mice. However, given that (i) the successful detection of this differential was dependent on the time of sampling and (ii) that TNF was only detected in the first 3-4 h post LPS challenge, we suggest that TNF may not be very useful as a prognostic marker in endotoxic shock. In contrast, circulating IL-6 appeared to mirror the symptoms of the endotoxic mice. The relative disappearance of IL-6 after 10 h in the non-lethally injected mice corresponded with their symptomatic recovery, while IL-6 continued to circulate up to the time of death in the lethally injected mice. Furthermore, there appeared to be a good correlation between the levels of injected LPS and the levels of IL-6 induced into the circulation. Our results suggest that IL-6, rather than TNF, may serve as a prognostic marker for endotoxic shock.
Kelly
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NM
Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, D.C.
Cross
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D000818:Animals; D015415:Biomarkers / Q000097:blood; D005260:Female; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D012772:Shock, Septic / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015415:Biomarkers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha