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Interleukin-8 (IL-8, CXCL8) was originally discovered as a powerful attractor and activator of polymorphonuclear leukocytes. It was soon recognized that IL-8 also affects proliferation and migration of cancer cells, tumor angiogenesis and metastasis, and that it is expressed in many cancerous cell types. IL-8 protein expression is usually increased in serum of cancer patients, but markedly higher concentrations are found in cancer-associated non-vascular extracellular fluids, such as pleural effusion, ascites and cyst fluid. Elevated concentrations of IL-8 are indicative of malignant processes also in cerebrospinal fluid, urine, saliva, interstitial fluid and cervicovaginal secretions. Higher IL-8 levels are typically found in high-grade peritumoral fluids rather than low-grade tumors and benign conditions, with the exception of inflammatory processes. In line with recent molecular biology investigations, it appears that the local IL-8 production is related to its malignant origin and to tumor progression. Hence, IL-8 in peritumoral fluid is to be taken into consideration while assessing tumor character and monitoring the tumor progression/remission status. Besides, the data here collected justify the attempts to find an IL-8-targeted inhibitory therapy more...

Besides massive expression in inflammatory pleural effusions, inflammatory markers are also present in cancerinduced pleural effusions. Recent advances in cancer biology point to a role of inflammatory signaling in cancer and encourage reconsidering the diagnostic and prognostic value of inflammatory markers. Here an attempt was made to relate protein levels of inflammatory markers to underlying malignant processes in the pleural space. Pleural effusions from lung cancer patients (n=116) were subjected to a multifactorial analysis covering 13 inflammatory markers. The composition of tumor-associated effusions was compared with that of parainflammatory pleural effusions (n=30), transudates (n=18), and serum values, and evaluated in relation to cancer origin, histology, cytology, pleural involvement, treatment history, and survival time. Inflammatory markers were significantly expressed in pleural effusions of paraneoplastic origin when compared to transudates and most serum levels. Values in pleura-invading and metastatic tumor-associated effusions were typically higher than those of other tumors. Many markers correlated negatively with survival, most prominently IL-8 (r=-0.36, p=0.001) and VEGF (r=-0.35, p=0.001). It appears that most inflammatory markers are highly expressed in tumor-associated pleural effusions, reflecting to some extent tumor origin and localization. Despite the lower efficacy of inflammatory markers in the differentiation between exudative pleural effusions, some inflammatory markers may represent potential prognostic markers of malignant processes in the pleural space. more...

Cathepsins S and H are present in immune cells and tissues and may play a role in the activation of an adoptive immune response. Our goal was to assess their protein levels in pleural fluids from 82 patients who underwent thoracentesis or thoracoscopy for therapeutic or diagnostic reasons and to relate them to an inflammatory, neoplastic or hemodynamic origin. Pleural effusions were also analyzed for a panel of 13 inflammatory or proliferative markers to test possible links to a nonspecific host reaction. Increased levels of cathepsin S were found in parainflammatory and cancer-related effusions compared to transudates. Cathepsin H levels were elevated only in parainflammatory effusions, whereas the levels in cancer-related effusions were comparable to transudates. Cathepsin S values significantly correlated with LDH, alpha-1-AT, VEGF, sICAM, sVCAM, MPO, uPA, MMP-9/TIMP-1, IL-8 and MCP-1, but not with CRP, IL-10 or cathepsin H. In contrast to cathepsin S, cathepsin H values did not correlate with markers of inflammation, indicating a specific role for cathepsin H in the pleural host response. In conclusion, the estimation of cathepsin S and cathepsin H may help to distinguish between effusions of different etiology. more...