ABSTRACT Introduction: our objective was to investigate the effects of the administration of pancreatic homogenates, with or without enzymatic activation, to healthy animals regarding cytokine serum levels and the development of pulmonary distress. Material and methods: 106 male Wistar rats, divided into three groups, were studied: group A, intraperitoneal administra- tion of homogenates activated with enterokinase; group B, ho- mogenates without enterokinase; and group C, control group with administration of physiological saline solution. Each group was di- vided into 4 subgroups according to the time of sacrifice: 0, 2, 6 and 24 hours. We studied the pulmonary and pancreatic histol- ogy, serum parameters of renal and hepatic function, and serum levels of IL-1β, IL-6 and TNFα. Results: there was no mortality in any group. Pancreatic disor- ders in A and B groups were noted at 24 hours. These two groups had statistically significant higher transaminase serum levels than those of the control group, as well as statistically significant higher creatinine levels in group A. IL-1β showed a statistically significant higher level at 6 h in both groups, A and B, but was higher in group A, which also exhibited significant pulmonary histologic damage with respect to controls at 6 h. Conclusions: the higher IL-1β level in group A may result from production by peritoneal macrophages under the influence of homogenate enzymatic activation. This may be the reason for lung damage. Key words: Pancreatic ascites. Pancreatic homogenates. Inter- leukin-1β. TNFα. Lung. Mozo G, del Olmo ML, Caro-Patón A, Reyes E, Manzano L, Belmonte A, Almaraz A, Álvarez-Mon M. Pulmonary injuries and cytokine levels after the intraperitoneal administration of pancreatic homogenates in rats. Rev Esp Enferm Dig 2004; 96: 527-538. INTRODUCTION During the course of severe acute pancreatitis (AP) the inflammatory process, which is initially localized and limit- ed to the pancreas, may spread with the induction of a sys- temic inflammatory response that can progress and even cause multiple organ failure (MOF) (1-3). In these cases, there is an accumulation of leukocytes, mainly polymor- phonuclear (PMN) cells, in various organs such as the kid- ney, liver and lung, in parallel to the severity of AP (4-6). The PMN adhesion process to vascular endothelial cells –and the subsequent extravasation and parenchymal infiltra- tion– is mediated by proinflammatory cytokines such as TNFα, IL-1β, IL-6 and IL-8. These are initially released from acinus cells and damaged peripancreatic tissues, and later produced in other organs (3,7-12). Many works have thoroughly studied the contribution of pancreatic ascites to the pathophysiology, development and degeneration of AP and its systemic involvement (13- 23). It has been demonstrated that during AP there is an increase in peritoneal permeability (24,25) that con- tributes to pancreatic enzyme transfer via the peritoneum to the thoracic duct (26). Moreover, in pancreatic ascites there are proinflammatory cytokines whose origin seems to be activated peritoneal macrophages (15,19,20,27), which contribute to the spreading of inflammation. Never- theless, these cytokines do not seem to be the only inflam- matory factors in ascites, since the latter will still induce systemic effects even in their absence (15,17-19,28-33). Peritoneal lavage has been proposed (34-36) as a measure to eliminate proinflammatory factors present in pancreatic ascites that may contribute to patient deterioration (1) by producing damaging effects on hemodynamics and organs such as the kidney, liver and lung (28,31,37-42). In the lung they can induce an adult respiratory distress syn- drome (ARDS), as observed in experimental models when injecting this exudate into the pulmonary artery (33) or following an intravenous (17) or intraperitoneal method (i.p.) (24). Pulmonary injuries and cytokine levels after the intraperitoneal administration of pancreatic homogenates in rats G. Mozo, M. L. del Olmo, A. Caro-Patón, E. Reyes 1 , L. Manzano 1 , A. Belmonte, A. Almaraz and M. Álvarez-Mon 1 Department of Medicine. University of Valladolid. Spain. 1 Department of Immunology. University of Alcalá de Henares. Madrid. Spain 1130-0108/2004/96/8/527-538 REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS Copyright © 2004 ARÁN EDICIONES, S. L. REV ESP ENFERM DIG (Madrid) Vol. 96. N.° 8, pp. 527-538, 2004 Recibido: 20-11-03. Aceptado: 27-01-04. Correspondencia: María Lourdes del Olmo Martínez. C/ Federico Landro- ve, 14, 3º. 47014 Valladolid. e-mail: delolmo@uva.es ORIGINAL PAPERS