Pediatric Pulmonology 45:1201–1204 (2010) Tumor Necrosis Factor Alpha in Experimental Empyema Thoracis Vanessa Feller Martha, PhD, 1 * Jose ´ Carlos Fraga, PhD, 2 Se ´ rgio Luis Amante ´a, PhD, 3 Paulo Sanches, PhD, 4 Jane Kulczynski, PhD, 5 Denise P. Machado, 6 and Fernanda Canani, MD 7 Summary. Purpose: To determine serum and pleural concentrations of tumor necrosis factor alpha (TNF-a) in an experimental model of empyema induced by intrapleural inoculation of Staphylococcus aureus or Streptococcus pneumoniae . Methods: Wistar rats were inoculated with S. aureus (SA group, 17 animals) or S. pneumoniae (SP group, 30 animals). The presence of free fluid or pus in the pleural space was investigated. TNF-a levels >150 pg/ml (minimum detection limit) were determined in pleural fluid and blood. Histopathological examination of pleural tissue was performed to determine the severity of infection. Results: Serum TNF-a was >150 pg/ml in nine SA versus 10 SP rats. In pleural fluid, TNF-a was >150 pg/ml in 11 SA versus 19 SP rats. Pleural and serum TNF-a concentrations were significantly different in the SP group (P ¼ 0.035), but not in the SA group (P ¼ 0.727). Pleural TNF-a was similar in both groups (P ¼ 0.92), but serum TNF-a was significantly higher in SA (P ¼ 0.03). Out of 17 SA animals, 1 (5.8%) did not develop empyema, versus 4 (13.3%) out of 30 SP animals. A mild inflammatory response was predominant in both groups, but the inflammatory process was significantly more severe in SP (P ¼ 0.012). However, TNF-a levels were not associated with severity of the inflammatory response. Conclusions: We describe a simple and effective rat model of empyema. TNF-a levels above 150 pg/ml in the pleural fluid are useful to confirm empyema, but cannot predict the severity of the inflammatory response. TNF-a levels below 150pg/ml are useful to rule out empyema. Pediatr Pulmonol. 2010; 45:1201–1204. ß 2010 Wiley-Liss, Inc. Key words: model experimental; Streptococcus pneumoniae; empyema. Funding source: FIPE (Research Incentive Fund) of HCPA; Centro de Pesquisa Experimental do Hospital de Clı ´nicas de Porto Alegre. INTRODUCTION The therapeutic management of parapneumonic pleural effusions in children is still controversial, and there is no consensus in the literature regarding the indication for thoracotomy, intrapleural administration of fibrinolytics, and video-assisted thoracoscopic surgery (VATS). 1,2 The difficulty in conducting prospective and controlled population-based studies to assess these treatment options has encouraged the development of experimental models. Early studies conducted in guinea pigs or rabbits were limited by the need for sophisticated thoracotomy equipment and ventilatory support, as well as by the high mortality rate of animals. 3–5 More recently, rabbit and rat models of thoracentesis-induced empyema using different inocula have resulted in lower morbidity and mortality, 6–8 so that more recent studies were able to evaluate inflammatory response with a focus on the establishment of significant relationships for clinical practice. 9–13 In empyema thoracis, bacterial invasion of the pleural space causes monocytes, macrophages, and other cells to release inflammatory mediators (cytokines). Tumor necrosis factor alpha (TNF-a) is one of the major cytokines released by this inflammatory reaction. TNF-a acts both locally and systemically. 9,10 1 Hospital Santo Anto ˆnio and Hospital Moinhos de Vento, Porto Alegre, RS, Brazil. 2 Department of Surgery, Universidade Federal do Rio Grande do Sul (UFRGS), Pediatric Thoracic Surgery Unit/Pediatric Surgery Service, Hospital de Clı ´nicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil. 3 Department of Pediatrics, Universidade Federal de Cie ˆncias da Sau ´de de Porto Alegre (UFCSPA), Hospital Santo Anto ˆnio, Porto Alegre, RS, Brazil. 4 Department of Biomedical Engineering, HCPA, Porto Alegre, RS, Brazil. 5 Department of Pathology, UFRGS and HCPA, Porto Alegre, RS, Brazil. 6 Unit of Microbiology and Molecular Biology, Division of Clinical Pathology, HCPA, Porto Alegre, RS, Brazil. 7 School of Medicine, UFRGS and HCPA, Porto Alegre, RS, Brazil. *Correspondence to: Vanessa Feller Martha, PhD, Rua Primeiro de Janeiro, 150, apt 1201, Torre 1, Porto Alegre, RS, Brazil. E-mail: vanessafeller@hotmail.com Received 5 October 2009; Revised 14 April 2010; Accepted 30 April 2010. DOI 10.1002/ppul.21308 Published online 23 July 2010 in Wiley Online Library (wileyonlinelibrary.com) ß 2010 Wiley-Liss, Inc.