The Reduction of Peripheral Blood CD4+ T Cell Indicates Persistent Organ Failure in Acute Pancreatitis

Zhiyong Yang, Yushun Zhang, Liming Dong, Chong Yang, Shanmiao Gou, Tao Yin, Heshui Wu, Chunyou Wang, Zhiyong Yang, Yushun Zhang, Liming Dong, Chong Yang, Shanmiao Gou, Tao Yin, Heshui Wu, Chunyou Wang

Abstract

Objective: Few data are available on the potential role of inflammatory mediators and T lymphocytes in persistent organ failure (POF) in acute pancreatitis (AP). We conducted a retrospective study to characterize their role in the progression of POF in AP.

Methods: A total of 69 AP patients presented within 24 hours from symptom onset developing organ failure (OF) on admission were included in our study. There were 39 patients suffering from POF and 30 from transient OF (TOF). On the 1st, 3rd and 7th days after admission, blood samples were collected for biochemical concentration monitoring including serum IL-1β, IL-6, TNF-α and high-sensitivity C-reactive protein (hs-CRP). The proportions of peripheral CD4(+) and CD8(+) T lymphocytes were assessed based on flow cytometry simultaneously.

Results: Patients with POF showed a significantly higher value of IL-1β and hs-CRP on day 7 compared with the group of TOF (P < 0.05). Proportions of CD4(+) T cells on days 1, 3, 7 and CD4(+)/ CD8(+) ratio on day 1 were statistically lower in the group of POF patients (P < 0.05). A CD4(+) T cell proportion of 30.34% on day 1 predicted POF with an area under the curve (AUC) of 0.798, a sensitivity with 61.54% and specificity with 90.00%, respectively.

Conclusions: The reduction of peripheral blood CD4(+) T lymphocytes is associated with POF in AP, and may act as a potential predictor.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Sequential changes in the values…
Fig 1. Sequential changes in the values of IL-1β (A), IL-6 (B), TNF-α (C) and hs-CRP (D) in the POF and TOF groups.
Fig 2. Sequential changes in the proportion…
Fig 2. Sequential changes in the proportion of CD4+ T lymphocytes (A), the proportion of CD8+ T lymphocytes (B) and CD4+ / CD8+ ratio (C) in the POF and TOF groups.
Data of CD4+ and CD8+ T cells were available in 26, 29 and 30 POF patients on days 1, 3 and 7, respectively.
Fig 3. ROC curve of CD4 +…
Fig 3. ROC curve of CD4+ T cell proportion versus CD4+/CD8+ ratio in predicting POF.
Fig 4. ROC curve of APACHE II…
Fig 4. ROC curve of APACHE II score on admission versus APACHE II score on day 1 in predicting POF.

References

    1. Oiva J, Mustonen H, Kylanpaa ML, Kyhala L, Kuuliala K, Siitonen S, et al. Acute pancreatitis with organ dysfunction associates with abnormal blood lymphocyte signaling: controlled laboratory study. Crit Care. 2010; 14: R207 10.1186/cc9329
    1. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62: 102–111. 10.1136/gutjnl-2012-302779
    1. Nawaz H, Mounzer R, Yadav D, Yabes JG, Slivka A, Whitcomb DC, et al. Revised Atlanta and determinant-based classification: application in a prospective cohort of acute pancreatitis patients. Am J Gastroenterol. 2013; 108: 1911–1917. 10.1038/ajg.2013.348
    1. Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut. 2004; 53: 1340–1344.
    1. Mofidi R, Duff MD, Wigmore SJ, Madhavan KK, Garden OJ, Parks RW. Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis. Br J Surg. 2006; 93: 738–744.
    1. Lytras D, Manes K, Triantopoulou C, Paraskeva C, Delis S, Avgerinos C, et al. Persistent early organ failure: defining the high-risk group of patients with severe acute pancreatitis? Pancreas. 2008; 36: 249–254. 10.1097/MPA.0b013e31815acb2c
    1. Sweeney KJ, Kell MR, Coates C, Murphy T, Reynolds JV. Serum antigen(s) drive the proinflammatory T cell response in acute pancreatitis. Br J Surg. 2003; 90: 313–319.
    1. Kylanpaa ML, Repo H, Puolakkainen PA. Inflammation and immunosuppression in severe acute pancreatitis. World J Gastroenterol. 2010; 16: 2867–2872.
    1. Nakayama S, Nishio A, Yamashina M, Okazaki T, Sakaguchi Y, Yoshida K, et al. Acquired immunityplays an important role in the development of murine experimental pancreatitis induced by alcohol and lipopolysaccharide. Pancreas. 2014; 43: 28–36. 10.1097/MPA.0b013e3182a7c76b
    1. Demols A, Le Moine O, Desalle F, Quertinmont E, Van Laethem JL, Deviere J. CD4(+) T cells play an important role in acute experimental pancreatitis in mice. Gastroenterology. 2000; 118: 582–590.
    1. Pietruczuk M, Dabrowska MI, Wereszczynska-Siemiatkowska U, Dabrowski A. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis. World J Gastroenterol. 2006; 12: 5344–5351.
    1. Halonen KI, Pettila V, Leppaniemi AK, Kemppainen EA, Puolakkainen PA, Haapiainen RK. Multiple organ dysfunction associated with severe acute pancreatitis. Crit Care Med. 2002; 30: 1274–1279.
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985; 13: 818–829.
    1. Working Party of the British Society of Gastroenterology, Association of Surgeons of Great Britain and Ireland, Pancreatic Society of Great Britain and Ireland, Association of Upper GI Surgeons of Great Britain and Ireland. UK guidelines for the management of acute pancreatitis. Gut. 2005; 54 Suppl 3: i1–i9.
    1. Group of Pancreas Surgery, Chinese Society of Surgery, Chinese Medical Association. The guideline of diagnosis and treatment of severe acute pancreatitis. Zhonghua Wai Ke Za Zhi. 2007; 45: 727–729.
    1. Johnson CD, Kingsnorth AN, Imrie CW, McMahon MJ, Neoptolemos JP, McKay C, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001; 48: 62–69.
    1. Mayer J, Rau B, Gansauge F, Beger HG. Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications. Gut. 2000; 47: 546–552..
    1. Curley PJ, McMahon MJ, Lancaster F, Banks RE, Barclay GR, Shefta J, et al. Reduction in circulating levels of CD4-positive lymphocytes in acute pancreatitis: relationship to endotoxin, interleukin 6 and disease severity. Br J Surg. 1993; 80: 1312–1315.
    1. Pezzilli R, Billi P, Beltrandi E, Maldini M, Mancini R, Morselli LA, et al. Circulating lymphocyte subsets in human acute pancreatitis. Pancreas. 1995; 11: 95–100.
    1. Uehara S, Gothoh K, Handa H, Tomita H, Tomita Y. Immune function in patients with acute pancreatitis. J Gastroen Hepatol. 2003; 18: 363–370.
    1. Bhatia M, Wong FL, Cao Y, Lau HY, Huang J, Puneet P, et al. Pathophysiology of acute pancreatitis. Pancreatology. 2005; 5: 132–144.
    1. Takeyama Y, Takas K, Ueda T, Hori Y, Goshima M, Kuroda Y. Peripheral lymphocyte reduction in severe acute pancreatitis is caused by apoptotic cell death. J Gastrointest Surg. 2000; 4: 379–387.
    1. Wilson PG, Manji M, Neoptolemos JP. Acute pancreatitis as a model of sepsis. J Antimicrob Chemother. 1998; 41 Suppl A: 51–63.
    1. Papachristou GI, Clermont G, Sharma A, Yadav D, Whitcomb DC. Risk and markers of severe acute pancreatitis. Gastroenterol Clin North Am. 2007; 36: 277–296.
    1. Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock KL. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med. 2007; 13: 851–856.
    1. Sendler M, Dummer A, Weiss FU, Kruger B, Wartmann T, Scharffetter-Kochanek K, et al. Tumour necrosis factor alpha secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice. Gut. 2013; 62: 430–439. 10.1136/gutjnl-2011-300771
    1. Tompkins RG. The role of proinflammatory cytokines in inflammatory and metabolic responses. Ann Surg. 1997; 225: 243–245.
    1. Aoun E, Chen J, Reighard D, Gleeson FC, Whitcomb DC, Papachristou GI. Diagnostic accuracy of interleukin-6 and interleukin-8 in predicting severe acute pancreatitis: a meta-analysis. Pancreatology. 2009; 9: 777–785. 10.1159/000214191
    1. Al MI. Severe acute pancreatitis: pathogenetic aspects and prognostic factors. World J Gastroenterol. 2008; 14: 675–684.
    1. Buter A, Imrie CW, Carter CR, Evans S, McKay CJ. Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis. Br J Surg. 2002; 89: 298–302.

Source: PubMed

3
Se inscrever