CYTOKINES AND SOLUBLE CYTOKINE RECEPTORS IN PLEURAL EFFUSIONS FROM SEPTIC AND NONSEPTIC PATIENTS

The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noni nfectious origin. To evaluate the impact of a lung and/or intrathoraci c infection in such a circumstance, we compared the levels of proinfla mmatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor an tagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, s TNFRII); and antiinflammatory cytokines (transforming growth factor-be ta [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 (slL-6R). Bronchoalveolar lavage fluids (B ALFs) were also studied in a few septic patients. High and nonsignific antly different levels of cytokines and inhibitors were detected in bo th groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pl eural effusion were higher than in plasma, whereas the levels of IL-1r a and slL-6R were higher in plasma. The levels of slL-6R influenced th e bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significan t correlation was observed for the soluble receptors slL-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 e ffusion (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 h ighest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independ ently of the presence of infection. Because cytokines can be trapped b y the surrounding cells in their environment, measurable levels of cyt okines in biologic fluids represent the ''tip of the iceberg,'' which is not the case for soluble receptors. The correlations of these latte r markers between plasma and pleura strongly suggest that exchanges be tween both compartments can occur in both directions.