Abstract 2187: The Balance Of Pro-inflammatory And Ant-inflammatory Circulating Cytokine mRNA Gene Expression In CHF Patients With And Without Cachexia Compared To Healthy Control Subjects.

Abstract

Background: Chronic heart failure (CHF) is a state of chronic inflammation. High serum levels of TNF alpha and the presence of cardiac cachexia are known to predict poor survival in CHF. Abnormal balance of pro- and anti-inflammatory circulating cytokine mRNA gene expression is thought to contribute to cachexia in humans, but has never been studied in CHF patients. Methods and Results: We studied 7 patients with cardiac cachexia (age 70±4 years, LVEF 28±2%, peak VO2 12.7±1.6 mL/kg/min, all >6% weight loss in previous 6–24 months), 19 noncachectic CHF patients (age 68±2 years, LVEF 31±2%, peak VO2 14.7±1.1 mL/kg/min) and 17 control subjects of similar age and gender (peak VO2 25.1±1.7 mL/kg/min, LVEF 71±2%). The mRNA gene expression of circulating mononuclear blood cells for pro-inflammatory mediators that have been implicated in the wasting process of ageing (TNF, STAT-1, STAT-3, SOCS-1 and SOCS-3) as well as anti-inflammatory cytokines (IL-10, tumor growth factor (TGF) beta were investigated by real time polymerase chain reaction. Values for the house keeping gene and genes of interest were calculated from double determinations within 40 cycles. We found higher TNF expression in cachectic compared to noncachectic CHF patients (log mean −0.5±0.17 vs. −1.2±0.12, p=0.002, ANOVA-p=0.0071) and control subjects (log mean −1.2±0.1, p=0.006). In contrast, there was no change in IL-10 gene expression in cachectic patients compared to noncachectic patients and controls (log mean −2.6±0.2 vs. −3.0±0.09 vs. −2.9±0.1, all p>0.13). Consequently TNF/IL-10 expression ratio was highest in cachectic patients (308±138 vs. 132±55 in noncachectic CHF patients vs. 101±37 in controls, p<0.004). There were no differences in gene expression of STAT-1, STAT-3, SOCS-1, SOCS-3 between cachectic and noncachectic individuals (all p>0.17). Similarly, no differences were found for gene expression of TGF beta (p>0.15). Conclusion: The balance between the pro-inflammatory cytokine TNF and the anti-inflammatory cytokine IL-10 on the level of mRNA expression of circulating mononuclear cells is significantly disturbed. Proinflammatory cytokine imbalance in cardiac cachexia may be important for the pathophysiology of body wasting and may represent the activated immune reflex.