Prognostic value of pro-inflammatory cytokine and pro-angiogenesis factor in differentiating malignant from benign exudative effusion Radwa Ahmed Elhefny 1 , Marwa Moawad Shaban 2 and Olfat Gamil Shaker 3 1 Department of Chest Diseases, Fayoum University, Cairo, Egypt 2 Department of Chest Diseases, Cairo University, Cairo, Egypt 3 Department of Chemical Biochemistry and Molecular Biology, Cairo University, Cairo, Egypt Abstract Background and Aims: The precise mechanism of pathogenesis in exudation of effusions is uncertain. Released factors in inflammation and malignancy of pleura are related to incremented permeability of the micro-pleural vessels. Angiopoietins (Ang) take part in development of angiogenesis and pleural inflammation. Interleukin-8 (IL-8) influences proliferation and tumor angiogenesis and it is expressed in cancer. The aims of this study were to investigate the relationship between inflammation, angiogenesis and etiologies of exudative effusions, and to evaluate the diagnostic value in differentiating malignant from benign. Methods: The study includes 49 pleural fluid (PF) samples. Ang-2 and IL-8 in PF and serum were estimated. Results: Ten patients were transudative and 39 patients were exudative fluid, sub- divided into 16 benign and 23 malignant effusion. Ang-2 and IL-8 either fluid level or ratio were in significantly high in exudative more than in transudative fluid (P = 0.002). Ang-2 and IL-8 in PF were in high level than in serum of exudative and transudative. Ang-2 fluid level and ratio were significantly high in benign exudative effusion (P = 0.01, P = 0.05, respectively), while IL-8 level was significantly high in malignant exudative effusion (P = 0.04). Cut-off points for PF Ang-2 and IL-8 in differentiating malignant from benign exudative were 15.67 ng/mL, 325.54 pg/mL, respectively. Conclusion: Our results support the evidence that angiogenesis and inflammatory pathways are linked, and that inflammation and vascular permeability of pleura constitutes the pathogenic basis of the majority of exudative effusion. Please cite this paper as: Elhefny RA, Shaban MM and Shaker OG. Prognostic value of pro-inflammatory cytokine and pro-angiogenesis factor in differentiating malig- nant from benign exudative effusion. Clin Respir J 2015; ••: ••–••. DOI:10.1111/ crj.12302. Key words angiopoietin-2 – diagnosis – exudative effusions – interleukin-8 – malignant effusion Correspondence Radwa Ahmed Elhefny, MD, Department of Chest Diseases, Fayoum University, 43 Gol Gamal Street-Elmohandseen-Giza, 12654 Cairo, Egypt. Tel: 201227453364 Fax: 0846302350 email: rah02@fayoum.edu.eg Received: 09 March 2014 Revision requested: 08 March 2015 Accepted: 23 March 2015 DOI:10.1111/crj.12302 Authorship and contributorship Contribution by all authors has been done during the planning, lay outing, analysis and clarification of data, outlining the paper or updating it critically for necessary rational content. All authors have approved the final version of the paper for submission. All authors had full access to all of the data in the study and take responsibility for the integrity of the data. All authors are responsible for the analysis of the data and its accuracy. Ethics This research was approved by the Scientific Research Ethics Committee [session No (1) on 25/3/2014] Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Summary at glance: We studied the pleural fluid and serum levels of angiopoietin-2 and interleukin-8 in order to explore correlation between inflammation and angiogenesis with different etiologies of exudative effusions in order to diagnose, differentiate malignant from benign effusion and improve diagnosis decision through comprehensive tools that help with differential diagnosis. Abbreviations: ADA adenosine deaminase Ang angiopoietins EGF endothelial growth factor ELISA enzyme-linked immunosorbent assay IL-8 interleukin-8 LDH lactate dehydrogenase ROC receiver operator characteristic SPSS Statistical Package for the Social Science VEGF vascular endothelial growth factor. The Clinical Respiratory Journal ORIGINAL ARTICLE 1 The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd