What Are Appropriate Controls for Cardiac Interleukin-6 Expression in Heart Failure?

To the Editor:We read with interest the report by Podewski et al 1 on the expression of interleukin-6 (IL-6) and related cytokines, their receptors, and molecules of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaltransduction cascade in patients with idiopathic dilated cardiomyopathy.We agree that in patients with dilated cardiomyopathy, the protein expression of IL-6 -related molecules and their signal-transduction cascade have not been evaluated before in such detail.However, we have some concerns.IL-6 and its receptor subunits have been extensively investigated before in failing hearts. 2,3 In one of our studies on the cardiac IL-6/IL-6 receptor system, we particularly emphasized the significance of the type of controls used. 4,5Nonfailing donor hearts showed expression levels of IL-6 receptor and glycoprotein (gp) 130 similar to those observed in failing hearts.Because these hearts were nonfailing donor hearts, just as those used by Podewski et al, 1 the lack of B-type natriuretic peptide upregulation apparently does not rule out upregulation of the cardiac IL-6 system, presumably related to brain death.In contrast, we could not detect IL-6, IL-6 receptor, and gp130 mRNAs in endocardial biopsies of patients with normal ventricular function. 4 Consequently, to test the hypothesis of stimulation of the IL-6/IL-6 receptor system in failing hearts, instead of comparing these with nonfailing donor hearts, biopsies of patients with normal ventricular function seem preferable.In light of these study design issues, the data of Podewski et al 1 should be interpreted with caution.