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Association of steroid use with complicated sigmoid diverticulitis: potential role of activated CD68+/CD163+ macrophages

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Abstract

Background

Immunosupression and, especially, intake of steroids have previously been identified as risk factors for complicated types of sigmoid diverticulitis. However, little is known about the underlying molecular and cellular mechanisms. We aimed to elucidate the potential role of activated macrophages in this respect.

Methods

A consecutive series of n = 101 patients having undergone surgical resection for sigmoid diverticulitis at our institution was analyzed regarding the inflammatory infiltrate and prevalence of comorbid diseases as well as risk factors, including steroid use. Fifty-seven patients had complicated types of diverticulitis with severe inflammation (group A). Forty-four patients had moderate inflammation, most of whom had been operated for chronically recurrent diverticulitis (group B). Randomly selected 50 patients (n = 20/group A/n = 30 group B) underwent immunolabelling against CD68 and CD163.

Results

Using immunofluorescence double labeling experiments we found a strong positive correlation of CD68 expression with CD163 expression (т = 0.934). High CD68 expression (x ≥ 23%) and high CD163 expression (x ≥ 22%) within stromal cells of the lamina propria was significantly associated with steroid use (CD68, p = 0.012 and CD163, p = 0.004, respectively) and complicated sigmoid diverticulitis with severe inflammation (CD68, p = 0.0001 and CD163, p = 0.001, respectively).

Conclusions

Inflammation, especially mediated by activated (CD68+/CD163+) macrophages in histopathological specimen might resemble the cellular link between steroid use and complicated types of sigmoid diverticulitis. Macrophages might be a suitable target for future supportive/preventive therapies. However, as long as we are lacking such strategies, we must bear in mind that steroid intake is a risk factor for complicated diverticulitis, especially when indicating surgical resection.

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References

  1. Jacobs DO (2007) Clinical practice. Diverticulitis. N Engl J Med 357(20):2057–2066. doi:10.1056/NEJMcp073228

    Article  PubMed  CAS  Google Scholar 

  2. Stollman NH, Raskin JB (1999) Diagnosis and management of diverticular disease of the colon in adults. Ad Hoc Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 94(11):3110–3121. doi:10.1111/j.1572-0241.1999.01501.x

    Article  PubMed  CAS  Google Scholar 

  3. Rafferty J, Shellito P, Hyman NH, Buie WD (2006) Practice parameters for sigmoid diverticulitis. Dis Colon Rectum 49(7):939–944. doi:10.1007/s10350-006-0578-2

    Article  PubMed  Google Scholar 

  4. Meagher AP, Frizelle FA, Janes S (2007) Practice parameters for sigmoid diverticulitis. Dis Colon Rectum 50(5):683–685. doi:10.1007/s10350-006-0856-z

    Article  PubMed  CAS  Google Scholar 

  5. Etzioni DA, Mack TM, Beart RW Jr, Kaiser AM (2009) Diverticulitis in the United States: 1998–2005: changing patterns of disease and treatment. Ann Surg 249(2):210–217. doi:10.1097/SLA.0b013e3181952888

    Article  PubMed  Google Scholar 

  6. Chapman J, Davies M, Wolff B, Dozois E, Tessier D, Harrington J, Larson D (2005) Complicated diverticulitis: is it time to rethink the rules? Ann Surg 242(4):576–581, discussion 581–573

    PubMed  Google Scholar 

  7. Bull DM, Bookman MA (1977) Isolation and functional characterization of human intestinal mucosal lymphoid cells. J Clin Invest 59(5):966–974. doi:10.1172/JCI108719

    Article  PubMed  CAS  Google Scholar 

  8. Golder JP, Doe WF (1983) Isolation and preliminary characterization of human intestinal macrophages. Gastroenterology 84(4):795–802

    PubMed  CAS  Google Scholar 

  9. Bockman DE, Boydston WR, Beezhold DH (1983) The role of epithelial cells in gut-associated immune reactivity. Ann NY Acad Sci 409:129–144

    Article  PubMed  CAS  Google Scholar 

  10. Sansonetti P (2001) Phagocytosis of bacterial pathogens: implications in the host response. Semin Immunol 13(6):381–390. doi:10.1006/smim.2001.0335

    Article  PubMed  CAS  Google Scholar 

  11. Kanai T, Ilyama R, Ishikura T, Uraushihara K, Totsuka T, Yamazaki M, Nakamuma T, Watanabe M (2002) Role of the innate immune system in the development of chronic colitis. J Gastroenterol 37(Suppl 14):38–42

    PubMed  CAS  Google Scholar 

  12. Bourlioux P, Koletzko B, Guarner F, Braesco V (2003) The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium “The Intelligent Intestine,” held in Paris, June 14, 2002. Am J Clin Nutr 78(4):675–683

    PubMed  CAS  Google Scholar 

  13. Lloberas J, Soler C, Celada A (1998) Dexamethasone enhances macrophage colony stimulating factor- and granulocyte macrophage colony stimulating factor-stimulated proliferation of bone marrow-derived macrophages. Int Immunol 10(5):593–599

    Article  PubMed  CAS  Google Scholar 

  14. Maniecki MB, Moller HJ, Moestrup SK, Moller BK (2006) CD163 positive subsets of blood dendritic cells: the scavenging macrophage receptors CD163 and CD91 are coexpressed on human dendritic cells and monocytes. Immunobiology 211(6–8):407–417. doi:10.1016/j.imbio.2006.05.019

    Article  PubMed  CAS  Google Scholar 

  15. Reichardt HM (2004) Immunomodulatory activities of glucocorticoids: insights from transgenesis and gene targeting. Curr Pharm Des 10(23):2797–2805

    Article  PubMed  CAS  Google Scholar 

  16. Lim HY, Muller N, Herold MJ, van den Brandt J, Reichardt HM (2007) Glucocorticoids exert opposing effects on macrophage function dependent on their concentration. Immunology 122(1):47–53. doi:10.1111/j.1365-2567.2007.02611.x

    Article  PubMed  CAS  Google Scholar 

  17. Liles WC, Dale DC, Klebanoff SJ (1995) Glucocorticoids inhibit apoptosis of human neutrophils. Blood 86(8):3181–3188

    PubMed  CAS  Google Scholar 

  18. Liu S, Russo PA, Baldassano RN, Sullivan KE (2009) CD68 expression is markedly different in Crohn’s disease and the colitis associated with chronic granulomatous disease. Inflamm Bowel Dis 15(8):1213–1217. doi:10.1002/ibd.20890

    Article  PubMed  Google Scholar 

  19. Billiau AD, Roskams T, Van Damme-Lombaerts R, Matthys P, Wouters C (2005) Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages. Blood 105(4):1648–1651. doi:10.1182/blood-2004-08-2997

    Article  PubMed  CAS  Google Scholar 

  20. Lau SK, Chu PG, Weiss LM (2004) CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol 122(5):794–801. doi:10.1309/QHD6-YFN8-1KQX-UUH6

    Article  PubMed  Google Scholar 

  21. Gattenlohner S, Waller C, Ertl G, Bultmann BD, Muller-Hermelink HK, Marx A (2003) NCAM(CD56) and RUNX1(AML1) are up-regulated in human ischemic cardiomyopathy and a rat model of chronic cardiac ischemia. Am J Pathol 163(3):1081–1090

    Article  PubMed  Google Scholar 

  22. Grimm M, Gasser M, Bueter M, Strehl J, Wang J, Nichiporuk E, Meyer D, Germer CT, Waaga-Gasser AM, Thalheimer A (2010) Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases. BMC Cancer 10:82. doi:10.1186/1471-2407-10-82

    Article  PubMed  Google Scholar 

  23. Chapman JR, Dozois EJ, Wolff BG, Gullerud RE, Larson DR (2006) Diverticulitis: a progressive disease? Do multiple recurrences predict less favorable outcomes? Ann Surg 243(6):876–883. doi:10.1097/01.sla.0000219682.98158.11, discussion 880–873

    Article  PubMed  Google Scholar 

  24. Holness CL, Simmons DL (1993) Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81(6):1607–1613

    PubMed  CAS  Google Scholar 

  25. Holness CL, da Silva RP, Fawcett J, Gordon S, Simmons DL (1993) Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family. J Biol Chem 268(13):9661–9666

    PubMed  CAS  Google Scholar 

  26. Travaglione S, Falzano L, Fabbri A, Stringaro A, Fais S, Fiorentini C (2002) Epithelial cells and expression of the phagocytic marker CD68: scavenging of apoptotic bodies following Rho activation. Toxicol In Vitro 16(4):405–411

    Article  PubMed  CAS  Google Scholar 

  27. Font MA, Fernandez A, Carvajal A, Gamez C, Badimon L, Slevin M, Krupinski J (2009) Imaging of early inflammation in low-to-moderate carotid stenosis by 18-FDG-PET. Front Biosci 14:3352–3360

    Article  PubMed  CAS  Google Scholar 

  28. Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI (2006) Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med 203(9):2073–2083. doi:10.1084/jem.20060245

    Article  PubMed  CAS  Google Scholar 

  29. Goerdt S, Bhardwaj R, Sorg C (1993) Inducible expression of MS-1 high-molecular-weight protein by endothelial cells of continuous origin and by dendritic cells/macrophages in vivo and in vitro. Am J Pathol 142(5):1409–1422

    PubMed  CAS  Google Scholar 

  30. Zwadlo G, Voegeli R, Osthoff KS, Sorg C (1987) A monoclonal antibody to a novel differentiation antigen on human macrophages associated with the down-regulatory phase of the inflammatory process. Exp Cell Biol 55(6):295–304

    PubMed  CAS  Google Scholar 

  31. Lederman ED, Conti DJ, Lempert N, Singh TP, Lee EC (1998) Complicated diverticulitis following renal transplantation. Dis Colon Rectum 41(5):613–618

    Article  PubMed  CAS  Google Scholar 

  32. Winkler J, Hochhaus G, Derendorf H (2004) How the lung handles drugs: pharmacokinetics and pharmacodynamics of inhaled corticosteroids. Proc Am Thorac Soc 1(4):356–363. doi:10.1513/pats.200403-025MS

    Article  PubMed  CAS  Google Scholar 

  33. Lipworth BJ, Jackson CM (2000) Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 23(1):11–33

    Article  PubMed  CAS  Google Scholar 

  34. Wiegers GJ, Croiset G, Reul JM, Holsboer F, de Kloet ER (1993) Differential effects of corticosteroids on rat peripheral blood T-lymphocyte mitogenesis in vivo and in vitro. Am J Physiol 265(6 Pt 1):E825–E830

    PubMed  CAS  Google Scholar 

  35. Dhabhar FS, McEwen BS (1999) Enhancing versus suppressive effects of stress hormones on skin immune function. Proc Natl Acad Sci USA 96(3):1059–1064

    Article  PubMed  CAS  Google Scholar 

  36. Zhou JY, Zhong HJ, Yang C, Yan J, Wang HY, Jiang JX (2011) Corticosterone exerts immunostimulatory effects on macrophages via endoplasmic reticulum stress. Br J Surg 97(2):281–293. doi:10.1002/bjs.6820

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank the assistance of Mrs. Manuela Schneider and Mrs. Sabine Gahn for their technical support. For S.K., the work was supported by the Wilhelm–Sander Foundation (grant no. 2007.068.1).

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Correspondence to Burkhard H. A. von Rahden.

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von Rahden, B.H.A., Kircher, S., Thiery, S. et al. Association of steroid use with complicated sigmoid diverticulitis: potential role of activated CD68+/CD163+ macrophages. Langenbecks Arch Surg 396, 759–768 (2011). https://doi.org/10.1007/s00423-011-0797-4

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  • DOI: https://doi.org/10.1007/s00423-011-0797-4

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