Mononuclear histocompatibility leukocyte antigen-DR expression in the early phase of acute pancreatitis

Abstract

Background: In acute pancreatitis (AP), several studies indicated that the balance between pro- and anti-inflammatory mediators is more important than the levels of proinflammatory response alone. This balance may be reflected by the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR, with a low concentration indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the time course of HLA-DR expression in the early phase of AP and the relationship to markers of inflammation, severity of the disease, organ function, septic complications and outcome during AP.

Methods: The expression of HLA-DR on peripheral monocytes was measured in 74 patients by flow cytometry and serum IL-6 was determined by using an immunochemiluminescence assay obtained 24 h, 48 h, 72 h, 7 days, 10 days and 14 days after admission in parallel with clinical data collection. 25 patients had mild disease (grade 1), 31 had severe disease but recovered without organ failure (grade 2) and 18 had severe disease and developed organ failure (grade 3).

Results: In 49 patients with severe disease, 11 patients suffered from sepsis, and 3 of them died during the hospital stay. During the first 14 days of AP, the percentage of HLA-DR in AP was significantly below the normal range of healthy subjects, it dropped to the lowest level on day 3, but then gradually recovered from the prophase depression. The HLA-DR expression decreased in the order grade 3 < grade 2 < grade 1 (p < 0.001). We also observed a significant inverse correlation between the percentage of HLA-DR+ and AP severity as assessed by APACHE-II scores (r = 0.754, p < 0.001) and MODS score (r = 0.675, p < 0.001). The peak of systemic inflammatory reaction, documented by maximum serum concentration of CRP, coincided with the nadir of HLA-DR suppression. Moreover, IL-6 and CRP serum concentrations were inversely correlated with HLA-DR expression over the entire observation period. Persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome.

Conclusion: Immune suppression develops early and rapidly in patients with AP, and the degree is parallel with the severity of the disease. Decreases in HLA-DR expression occurred simultaneously with signs of hyperinflammation in the early phase of AP, and persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome.