One of the interesting and novel findings in the study by Walter et al5is the relationship between serum IL-6 and FEV1. The “impact” of IL-6 on FEV1 was as large as that observed with CRP, and in lifetime nonsmokers its impact was even bigger. Biologically, IL-6 has a rather interesting function that makes it an attractive biomarker in COPD. IL-6 is the primary cytokine regulator of both CRP and fibrinogen in the liver. It also plays a critical role in hematopoiesis, causing thrombocytosis and leukocytosis with its overexpression.6 Interestingly, even during clinical stability, COPD patients have elevated blood levels of CRP, fibrinogen, leukocytes, and platelets compared with healthy control subjects.3 Since all of these molecules are regulated at least in part by IL-6, IL-6 may play a salient role in the systemic inflammatory responses in COPD. Furthermore, overexpression of IL-6 in serum or plasma has been associated with dyspnea,7skeletal muscle weakness,8insulin resistance,9pulmonary arterial hypertension,10and exacerbations.11Interestingly, in a murine model, IL-6 overexpression resulted in emphysema-like airspace enlargement and airway inflammation.12 The study by Walter et al5adds a critical piece of information that further supports the role of IL-6 as a potential biomarker in COPD: serum IL-6 is significantly related to reduced FEV1 independent of confounders such as age and smoking. However, before we can fully accept IL-6 as a relevant biomarker in COPD, several additional pieces of evidence are necessary. Firstly, since IL-6 can be produced by a wide variety of cells and organs including adipocytes, muscles, liver, and lungs,6 the predominant source of circulating IL-6 in COPD is unclear. It is imperative that future studies determine the lung contribution of IL-6 to the systemic pool in COPD during clinical stability as well as during exacerbations in order to ascertain the lung specificity of IL-6 measurements in serum. Secondly, large prospective studies are needed in COPD cohorts to determine whether IL-6 levels can indeed predict disease progression and health outcomes in COPD, independent of other well-established parameters such as smoking. Thirdly and most importantly, long-term interventional studies are required to determine whether IL-6 plays a causal or a bystander role in the pathogenesis and outcomes of COPD. The study by Walter and colleagues5 is provocative and interesting and has clearly put IL-6 at the center stage as a potential biomarker in COPD. Only time (and many additional studies) will determine whether IL-6 is the “real catch” or just a “red herring” as a biomarker in COPD.