Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis

Abstract

Leucocyte activation and proinflammatory cytokine release (tumour necrosis factor (TNF) and interleukin 6 (IL-6)) are thought to contribute to the induction of a systemic inflammatory response, an acute-phase response and multiple organ failure in patients with acute pancreatitis. The serum concentration of TNF, soluble TNF receptors (sTNFR55 and sTNFR75), IL-6 and C-reative protein (CRP) in 58 patients with acute pancreatitis was assessed during the first 2 days of admission. Thirty patients had mild disease and 28 severe disease, of whom 18 developed local pancreatic complications alone (Atlanta classification) and ten developed organ failure (a Goris score of 1 or more). TNF was detected in only 17 patients on the first day of admission, while soluble TNF receptors were detected in all patients and IL-6 in 34. On the first and second days of admission there was a progressive and significant (P < 0.03) increase in the median concentration of sTNFR55, sTNFR75 and IL-6 in patients eventually classified into those with mild disease, a local pancreatic complication alone, or organ failure. This pattern was also evident in CRP levels from the second but not the first day of admission. These findings suggest that proinflammatory cytokines or their soluble receptors may be more accurate early predictors of outcome than CRP, Moreover, markers of inflammation in the sera of patients with acute pancreatitis are highest in those who subsequently develop organ failure.

Interleucina-18 (IL-18) y otros parámetros inmunológicos como marcadores de gravedad en la pancreatitis aguda

“…Nos decidimos a determinar la IL-18, que algunos autores han considerado como marcador pronóstico de gravedad (14)(15)(16)(17)(18)(19)(20), así como el receptor-I soluble del TNF (sTNFRI) y el antagonista del receptor de la IL-1ß (IL1Ra) teniendo en cuenta, que en estudios previos (24), no se detectaron datos fiables en cuanto a los niveles séricos de sus correspondientes citocinas. En cuanto al sTNFRI, la significación estadística detectada a partir de las 48 horas que se mantiene a las 72 horas y a los 7 días, parece indicar que este pudiera tener valor pronóstico a partir del 2º día, lo cual se ha observado también en otros estudios donde se detecta elevación significativamente mayor del sTNFRI en relación con la gravedad, la existencia de necrosis pancreática y/o fallo multiorgánico (25)(26)(27)(28).…”

The regulatory role of immunosuppressants on immune abnormalities in acute pancreatitis

“…The release of copious amounts of inflammatory mediators leads to microcirculatory disturbances and leukocyte-mediated release of arachidonic acid metabolites, oxygen-free radicals, nitrogen-oxygen compounds and proteases. These secondary inflammatory mediators may cause organ and cell injury and the whole process may ultimately develop into systemic multiple organ dysfunction syndrome (MODS) (6)(7)(8).…”

Dexamethasone and dextran 40 treatment of 32 patients with severe acute pancreatitis

“…Recent studies [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] showed that inflammatory mediators and microcirculation disorders (MCD) play very important roles in the pathogenesis of severe acute pancreatitis. It has been proposed that the systemic sequelae of AP arise from excessive leukocyte activation with the release of secondary inflammatory mediators, such as interleukin (IL)-1α, IL-6, IL-8, IL-10; tumor necrosis factor-α (TNF-α); platelet-activating factor (PAF); nitric oxide (NO); and phospholipase A 2 [6][7][8][9][10][11][12][13][14] . Excessive production of these mediators contributes to the induction of the systemic inflammatory response syndrome, acute phase response, and multiple organ failure [7,14] .…”

“…It has been proposed that the systemic sequelae of AP arise from excessive leukocyte activation with the release of secondary inflammatory mediators, such as interleukin (IL)-1α, IL-6, IL-8, IL-10; tumor necrosis factor-α (TNF-α); platelet-activating factor (PAF); nitric oxide (NO); and phospholipase A 2 [6][7][8][9][10][11][12][13][14] . Excessive production of these mediators contributes to the induction of the systemic inflammatory response syndrome, acute phase response, and multiple organ failure [7,14] . On the other hand, the pancreatic microcirculation is impaired in acute pancreatitis [15] .…”