Effects of vacuum-assisted closure and Drotrecogin alpha on inflammatory markers in severe acute pancreatitis
Oscar Arias-Carvajal, José Manuel Hermosillo-Sandoval, Carlos Alberto Gutiérrez-Martínez, Fermín Paul Pacheco-Moisés, Genaro Gabriel Ortiz, Adolfo Daniel Rodríguez-Carrizalez, Luis Miguel Román-Pintos, Alejandra Guillermina Miranda-Díaz
Department of Chemistry, University of Guadalajara, Guadalajara, México.
Department of General Surgery, Specialties Hospital, National Occidental Medical Centre, Social Security Institute of México, Guadalajara, México.
Department of Physiology, University Health Sciences Centre, University of Guadalajara, Guadalajara, México.
Intensive Care Unit, Specialties Hospital, National Occidental Medical Centre, Social Security Institute of México, Guadalajara, México.
Occidental Biomedical Research Centre, Social Security Institute of México, Guadalajara, México.
DOI: 10.4236/abb.2013.48A2007   PDF    HTML   XML   3,402 Downloads   5,007 Views  


In severe acute pancreatitis (SAP) inflammatory processes foster necrosis, cellular lysis and liberation of vasoactive substances associated with multiple organ failure. The effects of vacuum-assisted closure and Drotrecogin alpha on inflammatory cytokines were evaluated in SAP patients with infected necrosis. Methods: Forty-six patients were included in three groups: Group 1, necrosectomy and abdominal cavity washing; Group 2, necrosectomy plus vacuum-assisted closure (VAC), and Group 3, necrossectomy plus VAC plus Drotrecogin alpha. Immunoreactive IL-32, TNF-α, IL-6, TGF-β and IL-2 cytokines were quantified with ELISA method. Results: IL-32 was significantly increased in all patients, predominantly the non-survivor of Group 3 (p < 0.0001). Group 2 maintained increased IL-32 levels throughout. Peak TNF-α was observed in non-survivors of Groups 1 and 2, with a frank tendency to decrease in Group 3. The IL-6 was increased, sustained throughout the study, peaking at the onset in non-survivors. At the end IL-6 tended to diminish, predominantly in survivors. TNF-α and IL-6 were significantly increased on hospitalization, with a maximum peak in non-survivors of all groups. Initial values of TGF-β were significantly increased in survivors of the three groups, and were significantly diminished in non-survivors; affecting pancreas regeneration and favoring systemic inflammation, with possible multiple-organ repercussions. IL-2 levels were elevated, predominantly in non-survivors of Group 1. There was positive correlation between the increase IL-32 and TNF-α, and negative correlation between the increase in TNF-α and decrease in TGF-β; and, a tendency for negative correlation between the IL-2 increased and TGF-β levels. Conclusion: We found a generalized, sustained inflammatory state that fosters a torpid outcome in SAP patients.

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Arias-Carvajal, O. , Hermosillo-Sandoval, J. , Gutiérrez-Martínez, C. , Pacheco-Moisés, F. , Ortiz, G. , Rodríguez-Carrizalez, A. , Román-Pintos, L. and Miranda-Díaz, A. (2013) Effects of vacuum-assisted closure and Drotrecogin alpha on inflammatory markers in severe acute pancreatitis. Advances in Bioscience and Biotechnology, 4, 43-53. doi: 10.4236/abb.2013.48A2007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Kamer, E., Unalp, H.R., Derici, H., Tansug, T. and Onal, M.A. (2007) Early diagnosis and prediction of severity in acute pancreatitis using the urine trypsinogen-2 dipstick test: A prospective study. World Journal of Gastroenterology, 13, 6208-6212. doi:10.3748/wjg.13.6208
[2] Bollen, T.L., van Santvoort, H.C., Besselink, M.G., van Leeuwen, M.S., Horvath, K.D., Freeny, P.C., et al. (2008) The Atlanta Classification of acute pancreatitis revisited. British Journal of Surgery, 95, 6-21. doi:10.1002/bjs.6010
[3] Aoun, E., Chen, J., Reighard, D., Gleeson, F.C., Whitcomb, D.C. and Papachristou, G.I. (2010) Diagnostic accuracy of interleukin-6 and interleukin-8 in predicting severe acute pancreatitis: A meta-analysis. Pancreatology, 9, 777-785. doi:10.1159/000214191
[4] Kim, S.H., Han, S.Y., Azam, T., Yoon, D.Y. and Dinarello, C.A. (2005) Interleukin-32: A cytokine and inducer of TNF-alpha. Immunity, 22, 131-142.
[5] Dambrauskas, Z., Giese, N., Gulbinas, A., Giese, T., Berberat, P.O., Pundzius, J., et al. (2010) Different profiles of cytokine expression during mild and severe acute pancreatitis. World Journal of Gastroenterology, 16, 1845-1853. doi:10.3748/wjg.v16.i15.1845
[6] Beutler, B. and Cerami, A. (1987) Cachectin: More than a tumor necrosis factor. The New England Journal of Medicine, 316, 379-385. doi:10.1056/NEJM198702123160705
[7] Zhang, H., Neuhofer, P., Song, L., Rabe, B., Lesina, M., Kurkowski, M.U., et al. (2013) IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality. Journal of Clinical Investigation, 123, 1019-1031. doi:10.1172/JCI64931
[8] Sandoval, D., Gukovskaya, A., Reavy, P., et al. (1996) The role of neutrophils and platelet—Activating factor in mediating experimental pancreatitis. Gastroenterology, 111, 1081-1091.
[9] Kilciler, G., Musabak, U., Bagci, S., Yesilova, Z., Tuzun, A., Uygun, A., et al. (2008) Do the changes in the serum levels of IL-2, IL-4, TNFalpha, and IL-6 reflect the inflammatory activity in the patients with post-ERCP pancreatitis? Clinical and Developmental Immunology, 2008, 481560. doi:10.1155/2008/481560
[10] Lempinen, M., Stenman, U.H., Finne, P., Puolakkainen, P., Haapiainen, R., Kemppainen, E. (2003) Trypsinogen-2 and trypsinogen activation peptide (TAP) in urine of patients with acute pancreatitis. Journal of Surgical Research, 111, 267-273. doi:10.1016/S0022-4804(03)00044-1
[11] Bucher, P., Pugin, F. and Morel, P. (2008) Minimally invasive necrosectomy for infected necrotizing pancreatitis. Pancreas, 36, 113-119. doi:10.1097/MPA.0b013e3181514c9e
[12] Besselink, M.G., van Santvoort, H.C., Boermeester, M.A., Nieuwenhuijs, V.B., van Goor, H., Dejong, C.H., et al. (2009) Timing and impact of infections in acutepancreatitis. British Journal of Surgery, 96, 267-273. doi:10.1002/bjs.6447
[13] Wondberg, D., Larusson, H.J., Metzger, U., Platz, A. and Zingg, U. (2008) Treatment of the open abdomen with the commercially available vacuum-assisted closure system in patients with abdominal sepsis. World Journal of Surgery, 32, 2724-2729. doi:10.1007/s00268-008-9762-y
[14] Jamdar, S. and Siriwardena, A.K. (2005) Drotrecoginalfa (recombinant human activated protein C) in severe acute pancreatitis. Critical Care, 9, 321-322. doi:10.1186/cc3777
[15] Pettila, V., Kyhala, L., Kylanpaa, M.L., Leppaniemi, A., Tallgren, M., Markkola, A., et al. (2010) APCAP-activatedprotein C in acutepancreatitis: A double-blind randomized human pilot trial. Critical Care, 14, R139. doi:10.1186/cc9203
[16] De Campos, T., Cerqueira, C., Kuryura, L., Parreira, J.G., Soldá, S., Perlingeiro, J.A., et al. (2008) Morbimortality indicators in severe acute pancreatitis. JOP, 9, 690-697.
[17] Cappell, M.S. (2008) Acute pancreatitis: Etiology, clinical presentation, diagnosis, and therapy. Medical Clinics of North America, 92, 889-923. doi:10.1016/j.mcna.2008.04.013
[18] Nishida, A., Andoh, A., Inatomi, O. and Fujiyama, Y. (2009) Interleukin-32 expression in the pancreas. The Journal of Biological Chemistry, 284, 17868-17876. doi:10.1074/jbc.M900368200
[19] Heinhuis, B., Koenders, M.I., van den Berg, W.B., Netea, M.G., Dinarello, C.A. and Joosten, L.A. (2012) Interleukin 32 (IL-32) contains a typical α-helix bundle structure that resembles focal adhesion targeting region of focal adhesion kinase-1. The Journal of Biological Chemistry, 287, 5733-5743. doi:10.1074/jbc.M111.288290
[20] Panek, J., Karcz, D., Pieton, R., Zasada, J., Tusinski M., Dolecki, M., et al. (2006) Blood serum levels of proinflammatory cytokines in patients with different degrees of biliary pancreatitis. Canadian Journal of Gastroenterology, 20, 645-648.
[21] Zhang, H., Patel, S.A., Kandil, E., Mueller, C.M., Lin, Y.Y. and Zenilman, M.E. (2003)Pancreaticelastase is proven to be a mannose-binding protein—Implications for the systemicresponse to pancreatitis. Surgery, 133, 678-688. doi:10.1067/msy.2003.175
[22] Jaffray, C., Mendez, C., Denham, W., Carter, G. and Norman, J. (2000) Specific pancreatic enzymes activate macrophages to produce tumor necrosis factor-alpha: Role of nuclear factor kappa B and inhibitory kappa B proteins. Journal of Gastrointestinal Surgery, 4, 370-377. doi:10.1016/S1091-255X(00)80015-3
[23] Mayer, J., Rau, B., Gansauge, F. and Beger, H.G. (2000) Inflammatory mediators in human acutepancreatitis: Clinical and pathophysiological implications. Gut, 47, 546-552. doi:10.1136/gut.47.4.546
[24] Friess, H., Lu, Z., Riesle, E., Uhl, W., Bründler, A.M., Horvath, L., et al. (1998) Enhanced expression of TGF-betas and their receptors in human acute pancreatitis. Annals of Surgery, 227, 95-104. doi:10.1097/00000658-199801000-00014
[25] Kihara, Y., Tashiro, M., Nakamura, H., Yamaguchi, T., Yoshikawa, H. and Otsuki, M. (2001) Role of TGF-beta1, extracellular matrix, and matrix metalloproteinase in the healing process of the pancreas after induction of acute necrotizing pancreatitis using arginine in rats. Pancreas, 23, 288-295. doi:10.1097/00006676-200110000-00010
[26] Zhang, X., Chez, H., Liu, F. and Zhang, J. (2009) Advances in researches on the immune dysregulation and therapy of severe acute pancreatitis. Journal of Zhejiang University Science B, 10, 493-498. doi:10.1631/jzus.B0820265
[27] Malek, T.R. (2008) The biology of interleukin-2. Annual Review of Immunology, 26, 453-479. doi:10.1146/annurev.immunol.26.021607.090357
[28] Fritz, S., Hartwig, W., Lehmann, R., Will-Schweiger, K., Kommerell, M., Hackert, T., et al. (2008) Phrophylactic antibiotic treatment is superior to therapy on-demand in experimental necrotising pancreatitis. Critical Care, 12, R141. doi:10.1186/cc7118
[29] Heinrich, S., Schafer, M., Rousson, V. and Clavien, P.A. (2006) Evidence-based treatment of acute pancreatitis. A look at established paradigms. Annals of Surgery, 243, 154-168. doi:10.1097/01.sla.0000197334.58374.70
[30] Wang, X., Cui, Z., Li, H., Saleen, A.F., Zhang, D., Miao, B., et al. (2010) Nosocomial mortality and early prediction of patients with severe acute pancreatitis. Journal of Gastroenterology and Hepatology, 25, 1386-1393. doi:10.1111/j.1440-1746.2010.06376.x
[31] Pearce, C.B., Gunn, S.R., Ahmed, A. and Johnson, C.D. (2006) Machine learning can improve prediction of severity in acute pancreatitis using admission values of APACHE II score and C-reactive protein. Pancreatology, 6, 123-131. doi:10.1159/000090032
[32] Perez, D., Wildi, S., Demartines, N., Bramkamp, M., Koehler, C. and Clavien, P.A. (2007) Prospective evaluation of vacuum-assisted closure in abdominal compartment syndrome and severe abdominal sepsis. Journal of the American College of Surgeons, 205, 586-592. doi:10.1016/j.jamcollsurg.2007.05.015
[33] Labler, L., Mica, L., Harter, L., Trentz, O. and Keel, M. (2006) Influence of VAC therapy on cytokines and growth factors in traumatic wounds. Zentralblatt für Chirurgie, 131, S62-S67. doi:10.1055/s-2006-921511

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