Abstract
Purpose
We studied macrophage migration inhibitory factor (MIF)-related neutrophil dysfunction in patients with ulcerative colitis (UC), under conditions of surgical stress, focusing in particular on total preoperative steroid dosages.
Methods
Neutrophils were isolated from peripheral blood samples obtained from 21 UC patients soon after radical surgery for UC. The patients were divided into two subgroups according to their total preoperative prednisolone dosages. The neutrophil phagocytosis, viable cell, and cell necrosis rates after exposure to Escherichia coli were evaluated by flow cytometry. The supernatant concentrations of mediators after exposure to E. coli were evaluated by enzyme-linked immunosorbent assay.
Results
There was a significant positive correlation between the levels of MIF and the total preoperative dosage of prednisolone. More viable neutrophils from the high-dosage steroid group patients than from the low-dosage steroid group patients tended to undergo necrosis, followed by the release of neutrophil elastase after exposure to E. coli. The levels of anti-inflammatory cytokines were not enhanced after E. coli stimulation, but the levels of proinflammatory cytokines in the supernatants of neutrophils from the high-dosage steroid group patients were increased significantly.
Conclusion
Steroid-overdosed UC patients with MIFrelated neutrophil dysfunction may be at increased risk of destructive local inflammation following surgery.
Similar content being viewed by others
References
Onaitis MW, Mantyh C. Ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: historical development and current status. Ann Surg 2003;238:S42–S48.
Fukuhara T, Egashira A, Imamura M, Ikegami T, Oki E, Soejima Y, et al. Proctocolectomy for colon cancer associated with ulcerative colitis a few months after living donor liver transplantation for primary sclerosing cholangitis: report of a case. Surg Today 2009;39:59–63.
Heuschen U, Hinz U, Allemeyer E, Autschbach F, Stern J, Lucas M, et al. Risk factors for ileoanal J pouch-related septic complications in ulcerative colitis and familial adenomatous polyposis. Ann Surg 2002;235:207–216.
Mantzoros I, Kanellos I, Demetriades H, Christoforidis E, Kanellos D, Pramateftakis MG, et al. Effects of steroid on the healing of colonic anastomoses in the rat. Tech Coloproctol 2004;8:s180–s183.
Miki C, Ohmori Y, Yoshiyama S, Toiyama Y, Araki T, Uchida K, et al. Factors predicting postoperative infectious complications and early induction of inflammatory mediators in ulcerative colitis patients. World J Surg 2007;31:522–529.
Yoshiyama S, Miki C, Okita Y, Araki T, Uchida K, Kusunoki M. Neutrophil-related immunoinflammatory disturbance in steroidoverdosed ulcerative colitis patients. J Gastroenterol 2008;43:789–797.
Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995;377:68–71.
Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 2003;3:791–800.
Gando S, Nishihira J, Kobayashi S, Morimoto Y, Nanzaki S, Kemmotsu O. Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome. Intensive Care Med 2001;27:1187–1193.
Lehmann LE, Novender U, Schroeder S. Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis. Intensive Care Med 2001;27:1412–1415.
Boyum A. Isolation of leucocytes. A two-phase system for removal of red cells with methylcellulose as erythrocyte-aggregating agent. Scand J Clin Lab Invest Suppl 1968;97:9–29.
Anton PA, Targan SR, Shanahan F. Increased neutrophil receptors for and response to the proinflammatory bacterial peptide formyl-methionyl-leucyl-phenylalanine in Crohn’s disease. Gastroenterology 1989;97:20–28.
Ziv Y, Church JM, Fazio VW, King TM, Lavery IC. Effect of systemic steroids on ileal pouch-anal anastomosis in patients with ulcerative colitis. Dis Colon Rectum 1996;39:504–508.
Miki C, Yoshiyama S, Okita Y, Araki T, Uchida K, Yanagi H, et al. Neutrophil priming as a surgery-related risk factor for postoperative infectious complications in patients with ulcerative colitis. Dig Surg 2006;23:179–185.
Baumann R, Casaulta C, Simon D, Conus S, Yousefi S, Simon H. Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway. FASEB J 2003;17:2221–2230.
Bloom B, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science 1966;153:80–82.
Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 1994;179:1895–1902.
Riedemann NC, Guo RF, Gao H, Sun L, Hoesel M, Hollmann TJ, et al. Regulatory role of C5a on macrophage migration inhibitory factor release from neutrophils. J Immunol 2004;173:1355–1359.
Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN, et al. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma. J Clin Invest 1998;101:2869–2874.
Fingerle-Rowson G, Koch P, Bikoff R, Lin X, Metz CN, Dhabhar FS, et al. Regulation of macrophage migration inhibitory factor expression by glucocorticoids in vivo. Am J Pathol 2003;162:47–56.
Roger T, David J, Glauser MP, Calandra T. MIF regulates innate immune responses through modulation of Toll-like receptor 4. Nature 2001;414:920–924.
Santos L, Hall P, Metz C, Bucala R, Morand EF. Role of macrophage migration inhibitory factor (MIF) in murine antigeninduced arthritis: interaction with glucocorticoids. Clin Exp Immunol 2001;123:309–314.
Ishiguro Y, Ohkawara T, Sakuraba H, Yamagata K, Hiraga H, Yamaguchi S. Macrophage migration inhibitory factor has a proinflammatory activity via the p38 pathway in glucocorticoidresistant ulcerative colitis. Clin Immunol 2006;120:335–341.
Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 1995;146:3–15.
Hatanaka E, Monteagudo PT, Marrocos MS. Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes. Clin Exp Immunol 2006;146:443–447.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Okita, Y., Miki, C., Yoshiyama, S. et al. Neutrophil dysfunction in steroid-overdosed patients with ulcerative colitis: Potential relevance of macrophage migration inhibitory factor to increased postoperative morbidity. Surg Today 41, 1504–1511 (2011). https://doi.org/10.1007/s00595-010-4505-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00595-010-4505-8