Cytokines and Soluble Cytokine Receptors in Pleural Effusions from Septic and Nonseptic Patients

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Abstract
The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noninfectious origin. To evaluate the impact of a lung and/or intrathoracic infection in such a circumstance, we compared the levels of proinflammatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor antagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, sTNFRII); and antiinflammatory cytokines (transforming growth factor-beta [TGF-beta]) in pleural effusion and plasma from septic (n = 15) and nonseptic (n = 9) patients. In addition, we analyzed the levels of IL-6 and its soluble receptor (sIL-6R). Bronchoalveolar lavage fluids (BALFs) were also studied in a few septic patients. High and nonsignificantly different levels of cytokines and inhibitors were detected in both groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pleural effusion were higher than in plasma, whereas the levels of IL-1ra and sIL-6R were higher in plasma. The levels of sIL-6R influenced the bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significant correlation was observed for the soluble receptors sIL-6R (r = 0.67, p < 0.001), sTNFRI (r = 0.76, p < 0.001) and sTNFRII (r = 0.66, p = 0.001). Furthermore, a high correlation was found between the levels of both forms of sTNFRs in plasma (r = 0.95, p < 0.001) and in pleural effusion (r = 0.79, p < 0.001). In addition, a correlation was observed between the levels of TGF-beta in pleural effusion and in BALF. The highest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independently of the presence of infection. Because cytokines can be trapped by the surrounding cells in their environment, measurable levels of cytokines in biologic fluids represent the "tip of the iceberg," which is not the case for soluble receptors. The correlations of these latter markers between plasma and pleura strongly suggest that exchanges between both compartments can occur in both directions.

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