LETTER TO THE EDITOR
Plasma concentrations of bacterial lipopolysaccharide: A marker of infection or inflammation?
Mathias Rauchhaus, MDa and
Stefan D. Anker, MD, PhDb
a Klinik und Poliklinik für Innere Medizin III Martin-Luther-Universität Halle, Germany
b Department of Clinical Cardiology National Heart and Lung Institute Dovehouse Street London SW3 6LY, United Kingdom
The article by Wiedermann et al. (1) sheds more light on the potential importance of elevated plasma concentrations of bacterial lipopolysaccharide (LPS). This is, however, not the first published report on elevated LPS concentrations in cardiovascular disease. We proposed in 1997 that raised LPS plasma concentrations (potentially as a consequence of intestinal translocation) might be expected in patients with chronic heart failure (CHF) (2). Recently, we have demonstrated that low grade but significant endotoxemia is present in edematous patients with CHF, which was lowered after diuretic treatment (3).
Wiedermann et al. (1) discuss the importance of chronic and potentially repetitive infection as a cause for atherosclerosis. We would like to ask the authors which clinical signs of acute or chronic infection have or have not been documented in their study group at the time of the initial investigation. Was the measurement of body temperature included in the clinical evaluation protocol? If there were patients with clinical signs of an ongoing infection, did they have higher LPS plasma concentrations than noninfected patients? Did the study’s principal results of the relation between LPS and atherosclerosis remain the same after exclusion of these patients? How often was the diagnosis of infection based on biochemical measurements such as C-reactive protein (CRP) alone? CRP is an acute-phase protein, and primarily it is a sign of inflammation. Noninfectious processes such as hypoxia have been shown to cause inflammatory cytokine activation (4), which in turn can raise CRP levels (5). The presence of LPS in the bloodstream does not necessarily indicate the presence of bacteria in the circulation or bacterial infection. An alternative hypothesis to explain raised LPS levels in some patients in the study (1) could be that bacterial translocation across the intestinal wall occurs, potentially due to atherosclerotic processes in the mesenteric vasculature, contributing to local tissue ischemia.
The report raises another very important point. To date, there is no consensus on how to measure plasma LPS concentrations. In contrast to the methodology applied by Wiedermann et al. (1), we use LPS-free vacuum blood collection tubes (Endot Tube ET, Chromogenix, Mölndal, Sweden) (3). These tubes have been developed specifically for the measurement of LPS plasma concentrations. After centrifugation, these tubes can be stored directly in a freezer. This eliminates the aliquoting process at the time of sampling in the clinic, which is thought to be the main source of contamination. The processing of the samples can then be performed under sterile laboratory conditions at the time of LPS analysis. The use of standard tubes for the assessment of LPS concentrations in blood may need validation.
We agree with Wiedermann et al. (1) and Carlquist (6) that the pathophysiologic importance of bacterial LPS may potentially be transferable to a much broader spectrum of clinical conditions beyond sepsis. Although endotoxin antibodies have failed in septic patients, they may be of value in patients with cardiovascular diseases.
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References
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- Wiedermann CJ, Kiechl S, Dunzendorfer S, et al. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck study. J Am Coll Cardiol. 1999;34:1975–1981[Abstract/Free Full Text]
- Anker SD, Egerer KR, Volk HD, Kox WJ, Poole-Wilson PA, Coats AJ. Elevated soluble CD14 receptors and altered cytokines in chronic heart failure. Am J Cardiol. 1997;79:1426–1430[CrossRef][Medline]
- Niebauer J, Volk HD, Kemp M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet. 1999;353:1838–1842[CrossRef][Medline]
- Yan SF, Tritto I, Pinsky D, et al. Induction of interleukin 6 (IL-6) by hypoxia in vascular cells: central role of the binding site for nuclear factor-IL-6. J Biol Chem. 1995;270:11463–11471[Abstract/Free Full Text]
- Ganapathi MK, Rzewnicki D, Samols D, Jiang SL, Kushner I. Effect of combinations of cytokines and hormones on synthesis of serum amyloid A and C-reactive protein in Hep 3B cells. J Immunol. 1991;147:1261–1265[Abstract]
- Carlquist JF. Endotoxin: another phantom menace? J Am Coll Cardiol. 1999;34:1982–1984[Free Full Text]
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