Endocrine Abstracts (2005) 9 P31

Elevated endotoxin levels as a mediator of consistent chronic sub-clinical inflammation in CABG patients

AR Baker1, NF da Silva1, A Ranasinghe2, D Pagano2, RS Bonser2, S Kumar1 & PG McTernan1

1Unit for Diabetes & Metabolism, Warwick Medical School, University of Warwick, Clinical Sciences Building, Walsgrave Hospital, Coventry, UK; 2Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, Birmingham, UK.

Chronic sub-clinical inflammation is associated with increased risk of type 2 diabetes and cardiovascular disease. Patients undergoing CABG are at high risk of further cardiovascular events and also demonstrate sub-clinical inflammation. We therefore investigated alterations in the relative balance between pro-inflammatory agents, such as hsCRP versus changes in anti-inflammatory factors (adiponectin) and as such the potential molecular pathways mediating these changes. The aims of this study were to assess whether circulating endotoxin may represent a potential trigger for immune activation in this cohort (LERC approved). We firstly investigated endotoxin levels in BMI matched healthy lean case controls (CC) subjects (Age:43.0plus/minusSD 10.6yrs; BMI:29.6plus/minusSD 4.7kilograms per meter 2; n=27) compared with CABG subjects (Age:62.9plus/minusSD 15.2yrs; BMI:29.1plus/minusSD 3.8kilograms per meter 2 n=27) using a Limulus Amoebocyte Lysate gram negative endotoxin ELISA; secondly assessed the soluble CD14 levels (an immunological receptor involved in the presentation of LPS to the toll-like receptors) also by ELISA. Finally we also examined changes on CABG patients in hsCRP, sCDI4, TNFRII and adiponectin serum levels. The findings from this study demonstrated that endotoxin levels were significantly higher in CABG than controls (CABG: 6.7(meanplus/minusSD)2.3International Units per millilitre vs CC:0.88plus/minus0.33International Units per millilitre, pless than0.001). HsCRP was significantly raised in CABG patients (hsCRP: CABG: 9.11(meanplus/minusSEM) 0.92 vs CC: 1.27plus/minus0.55; pequals0.001). However, neither sCDI4 nor TNFRII were raised (sCD14: CABG:1359.1plus/minus203.2nanograms per millilitre vs CC:1487.5.1plus/minus429.7nanograms per millilitre, p=NS). Nevertheless adiponectin levels were significantly reduced in CABG patients (CABG:6.22plus/minus6.1milligrams per millilitre vs CC:29.01plus/minus6.09milligrams per millilitre, pequals0.013). In conclusion, endotoxin levels were significantly raised in CABG. In addition, the associated endotoxaemia may mediate chronic inflammation observed by raised hsCRP levels. The process mediating elevated hsCRP also results in reduction in adiponectin. Whilst sCD14 and TNFRII were unaltered this may suggest these factors may correlate with the early developmental phases of this disease. Taken together these data imply that endotoxaemia may mediate the alteration in the inflammatory risk profile and could ultimately reduce anti-inflammatory cytokines.

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