Decreased Proinflammatory Cytokines Production in Children with Complicated Parapneumonic Pleural Effusion after Intrapleural Fibrinolytic Treatment Jieh-Neng Wang, 1,2 Jyh-Wei Shin, 3 Tsuey-Yu Chang, 3 Jiu-Yao Wang, 2 and Jing-Ming Wu 2,4 Abstract—Intrapleural fibrinolytic therapy (IFT) provides clinical benefit in the treatment of complicated pleural parapneumonic effusion (CPE). Whether IFT influences the proinflamma- tory cytokines production and fibrinlytic activity is currently unclear. Therefore, we collected pleural effusion samples from CPE patients with IFT (study group) and patients without IFT (control group). A membrane human inflammatory cytokines array kit was used to compare the difference of targeted cytokine production between these two groups. Enzyme-linked immu- nosorbent assay (ELISA) methods were used for quantitative analysis of targeted cytokines and fibrinolytic enzymes. The results showed there were no significant differences between the study (n = 16) and control (n = 14) groups in patients’ demographic data. After fibrinolytic therapy, the patients in the study group had significant lower plasminogen activator inhibitor (PAI) level (732.36±254.09 ng/mL vs 1,509.36 ± 1,340.11 ng/mL, p <0.05) and higher urokinase plasminogen activator (u-PA) level (75.56±41.70 ng/mL vs 6.87±5.07 ng/mL, p <0.05) than they did before treatment. Moreover, the tissue inhibitors of metalloproteinase-2 (TIMP-2) (1,560.03±403.49 pg/mL vs 3,686.45±1,263.83 pg/mL, p <0.05) and inflammatory chemokine, regulated on activation normal T-cell expressed and secreted/chemokine (C-C motif) ligand 5 (RANTES), (293.58±212.93 pg/mL vs 749.27±53.79 pg/mL, p <0.05), were also significantly lower in the study group after fibrinolytic therapy, but not in the control group. In conclusion, intrapleural fibrinolytic treatment with urokinase could enhance fibrinolytic activity and decrease TIMP-2 and RANTES production. KEY WORDS: empyema; parapneumonic effusion; intrapleural fibrinolytic treatment; fibrinolytic activity; inflammatory cytokines; cytokines array assay. INTRODUCTION Fibrin formation and deposition are the hallmarks of pleural inflammation [1], which may enhance the release of proinflammatory cytokines in pleural fluid [2, 3]. Failure to control the pleural process may lead to progressive disease and can result in complicated parapneumonic effusions (CPE) [4]. Fibrin turnover in the pleural cavity is greatly affected by the activity of fibrinolysis. The formation of key enzyme in fibrinolysis, plasmin, is based on the equilibrium between plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs) [5]. Proinflamma- tory cytokines may reduce fibrinolytic activity by stimulat- ing the release of PAI-1 and result in an imbalance between PAI-1 and two PAs, tissue PA (t-PA) and urokinase PA (u-PA) in the pleural cavity. This imbalance leads to fibrin formation and deposition and subsequent loculation of the 1 Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan 70421, Taiwan 2 Department of Pediatrics, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 70428, Taiwan 3 Department of Parasitology, National Cheng Kung University Medical College, Tainan 70421, Taiwan 4 To whom correspondence should be addressed at Department of Pediatrics, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 70428, Taiwan. E-mail: jingming@mail.ncku.edu.tw 0360-3997/09/0600-0410/0 # 2009 Springer Science + Business Media, LLC Inflammation, Vol. 32, No. 6, December 2009 ( # 2009) DOI: 10.1007/s10753-009-9150-2 410