In a recent issue of CHEST, Inoue and colleagues (October 2003)1disagreed with the results of a study by Carpagnano and colleagues2 regarding the role of interleukin (IL)-6 in the pathogenesis of obesity and obstructive sleep apnea syndrome (OSAS). In 2002, Carpagnano and colleagues2 reported that the measurement of IL-6 and 8-isoprostane levels, which indicate inflammation and oxidative stress in the airways of OSAS patients, may prove to be useful in screening and monitoring obese patients who have a high risk of developing OSAS. However, Inoue and colleagues1 suggested that further experimental and clinical studies are needed to establish the role of IL-6 in OSAS as well as obesity, not only as a diagnostic tool, but also as a therapeutic target. We basically agree with the authors that IL-6 affects the pathogenesis of obesity, obstructive sleep apnea, and metabolic disease. The proinflammatory cytokines may not always be the only specific cause of the pathogenesis of sleep apnea. However, some clinical data strongly indicate that IL-6 levels are elevated in patients with OSAS, but not in obese subjects.3–6 In our data, the mean (± SD) plasma level of IL-6 is greater in OSAS patients (7.3 ± 1.0 ng/mL) than in obese patients without OSAS (3.4 ± 0.6 ng/mL).3More importantly, we and other investigators have reported that the increased levels of IL-6 in patients with OSAS significantly decreases after treatment with nasal continuous positive airway pressure (nCPAP) [Table 1]. It indicates that obstructive sleep apnea itself contributes to the increased levels of proinflammatory cytokines and systemic inflammation. Interestingly, the spontaneous production of IL-6 by monocytes isolated from patients with OSAS is also elevated and is decreased by nCPAP therapy.4 This evidence may explain in part the increased concentrations of proinflammatory cytokines, including IL-6, in the airways of OSAS patients. Furthermore, the plasma levels of tumor necrosis factor (TNF)-α) and high-sensitivity C-reactive protein (hsCRP) are also elevated in patients with OSAS. IL-6 and hsCRP levels were independently associated with OSAS severity, as indicated by the apnea-hypopnea index. Furthermore, the plasma levels of IL-6 and TNF-α are associated with the levels of hsCRP, suggesting that increased numbers of proinflammatory cytokines are involved in that mechanism causing elevated levels of hsCRP in these patients. These data support the notion that inflammatory processes are activated in atherosclerotic lesions in patients with OSAS. Although hsCRP is a good marker of cardiovascular complication,7 other inflammatory mediators also are involved in atherosclerosis. In addition, the antagonism of IL-6 improves the endothelial function, suggesting that CRP and IL-6 synergistically affect endothelial dysfunction. Conceivably, hsCRP and other inflammatory cytokines accelerate the progression of atherosclerosis in patients with OSAS.