Triggering receptor expressed on myeloid cells-1 expression on monocytes is associated with inflammation but not with infection in acute pancreatitis

Abstract

Introduction: Acute pancreatitis (AP) is usually a mild and self-limiting disease, but some patients develop a severe form that is associated with high mortality. In AP, local inflammation is followed first by the systemic inflammatory response syndrome and then by the compensatory anti-inflammatory response syndrome, which is defined by low human leukocyte antigen (HLA)-DR expression on monocytes, increased concentration of the anti-inflammatory cytokine IL-10, and decreased monocyte function. Our aim was to measure the expression of triggering receptor expressed on myeloid cells (TREM)-1 (a proposed marker of infection or inflammation) and HLA-DR on monocytes, and the serum concentrations of IL-6 (a proinflammatory cytokine) and IL-10 in patients with AP to determine whether these markers can identify patients at high risk of developing severe AP or infection.

Methods: Fifty healthy volunteers, 18 patients with mild AP, and 11 patients with severe AP were included in this study. Samples were taken at admission and one and three days later. TREM-1 and HLA-DR expression was evaluated by flow cytometry, and soluble TREM-1, IL-6 and IL-10 concentrations were measured by ELISA.

Results: TREM-1 expression was higher in patients with AP than in healthy volunteers, but there was no difference between patients with mild and severe AP. TREM-1 expression was not associated with mortality or with the presence of infection. Soluble TREM-1 concentration in serum was higher in non-survivors than in survivors. HLA-DR expression was lower and IL-6 concentration higher in patients with severe AP and in infected patients.

Conclusions: Increased TREM-1 expression was associated with the presence of inflammation but not infection in AP. In patients with AP, low HLA-DR expression and high IL-6 concentration could predict severity and infection in samples taken shortly after admission.

Figure 1

TREM-1 expression was higher in patients with AP, but this increase was not associated with mortality, or with the presence of infection. (a) Triggering receptor expressed on myeloid cells-1 (TREM-1) expression was measured on blood monocytes from patients with mild acute pancreatitis (AP; n = 18), patients with severe AP (n = 11), and healthy volunteers (n = 50). Samples were taken from patients on admission (day 0) and one and three days later. One patient with mild AP was discharged from the hospital before the third blood sample was taken, and one patient with severe AP died after the first blood sample was collected. (b) Patients with AP were grouped according to survival (24 of these patients survived and 5 died). (c) Patients with AP were grouped according to the presence of infection (5 of the 29 patients developed infection). (d) Soluble TREM-1 expression was measured in the serum of patients with AP, which were grouped according to survival. * P < 0.05, ** P < 0.01, *** P < 0.001; the signs over each bar represent comparisons vs. healthy volunteers (H). MFI = mean fluorescence intensity.

Figure 2

HLA-DR expression was lower in patients with severe AP and in infected patients (a) Human leukocyte antigen (HLA)-DR expression was measured on blood monocytes from patients with mild acute pancreatitis (AP; n = 18), patients with severe AP (n = 11), and healthy volunteers (n = 50). Samples were taken from patients on admission (day 0) and one and three days later. One patient with mild AP was discharged from the hospital before the third blood sample was taken, and one patient with severe AP died after the first blood sample was collected. (b) Patients with AP were grouped according to survival (24 of these patients survived and 5 died). (c) Patients with AP were grouped according to the presence of infection (five of the 29 patients developed infection). * P < 0.05, ** P < 0.01, *** P < 0.001; the signs over each bar represent comparisons vs. healthy volunteers (H).

Figure 3

IL-6 concentration was higher in patients with severe AP and in infected patients. IL-6 concentration was measured in serum from patients with mild acute pancreatitis (AP; n = 18), patients with severe AP (n = 11), and healthy volunteers (n = 36). Samples were taken from patients on admission (day 0) and one and three days later. (a) Patients with mild and severe AP, (a) survivors and non-survivors, and (c) infected and non-infected patients are shown. * P < 0.05, ** P < 0.01, *** P < 0.001; the signs over each bar represent comparisons vs. healthy volunteers (H).

Figure 4

IL-10 concentration was higher in patients with severe AP and in infected patients. IL-10 concentration was measured in serum from patients with mild acute pancreatitis (AP; n = 18), patients with severe AP (n = 11), and healthy volunteers (n = 19). Samples were taken from patients on admission (day 0) and one and three days later. (a) Patients with mild and severe AP, (b) survivors and non-survivors, and (c) infected and non-infected patients are shown. * P < 0.05, ** P < 0.01, *** P < 0.001; the signs over each bar represent comparisons vs. healthy volunteers (H).