Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis

Leser, H. G.; Groß, Volker; Scheibenbogen, Carmen; Heinisch, Annika; Salm, R.; Lausen, M; Rückauer, K; Andreesen, Reinhard; Farthmann, E. H.; Schölmerich, Jürgen

doi:10.1016/0016-5085(91)90539-w

Cited by 326 publications

(153 citation statements)

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“…In human SAP, serum IL-6 is a reliable marker for AP severity, but its significance in mediating ALI is unknown (12). To examine the function of IL-6 in ALI genetically, we applied this modified model to mice deficient in IL-6.…”

Section: A Model For Sap-induced Lethal Alimentioning

confidence: 99%

“…In an attempt to identify surrogate parameters as predictors for complicated AP, several association studies linking cytokines and chemokines with AP severity have been conducted (11). Among these, serum levels of IL-6 and the IL-6-dependent acute phase protein C-reactive protein (CRP) were identified as the most reliable parameters for SAP (12,13). Research has yet to establish whether IL-6 or CRP are merely markers or have any pathophysiological impact.…”

Section: Introductionmentioning

confidence: 99%

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IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality

et al. 2013

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Acute lung injury (ALI) is an inflammatory disease with a high mortality rate. Although typically seen in individuals with sepsis, ALI is also a major complication in severe acute pancreatitis (SAP). The pathophysiology of SAP-associated ALI is poorly understood, but elevated serum levels of IL-6 is a reliable marker for disease severity. Here, we used a mouse model of acute pancreatitis-associated (AP-associated) ALI to determine the role of IL-6 in ALI lethality. Il6-deficient mice had a lower death rate compared with wild-type mice with AP, while mice injected with IL-6 were more likely to develop lethal ALI. We found that inflammation-associated NF-κB induced myeloid cell secretion of IL-6, and the effects of secreted IL-6 were mediated by complexation with soluble IL-6 receptor, a process known as trans-signaling. IL-6 trans-signaling stimulated phosphorylation of STAT3 and production of the neutrophil attractant CXCL1 in pancreatic acinar cells. Examination of human samples revealed expression of IL-6 in combination with soluble IL-6 receptor was a reliable predictor of ALI in SAP. These results demonstrate that IL-6 trans-signaling is an essential mediator of ALI in SAP across species and suggest that therapeutic inhibition of IL-6 may prevent SAP-associated ALI. IntroductionAcute pancreatitis (AP) accounts for more than 220,000 hospital admissions in the United States each year. Risk factors for AP include gallstones and excessive alcohol use. Interestingly, 70%-80% of AP patients develop mild and uncomplicated AP, while 20%-30% will develop more severe symptoms with concomitant multiple organ failure (MOF) (1). MOF is a consequence of the systemic activation of the immune system, known as systemic inflammatory response syndrome (SIRS). The clinical and pathological features of SIRS mimic those of sepsis; however, efforts to identify any infecting organisms in many patients with SIRS have failed (2-4). Although this syndrome is typically seen in individuals with sepsis, SIRS also occurs in patients with severe AP (SAP), blunt trauma, aseptic burns, and widespread surgical manipulations (5, 6). A major complication during SAP is acute lung injury (ALI). Nevertheless, the clinical course of ALI in SAP is still unpredictable and has a mortality rate of up to 50%. Current therapeutic approaches in SAP and associated ALI are symptomatically based (1, 7).The pathophysiology of SAP with ALI is poorly understood. Researchers have long hypothesized that SAP results from activation of digestive enzymes within the pancreas, a process called autodigestion (8). Indeed, inherited mutations in genes encoding for digestive enzymes have been found in patients with a hereditary form of pancreatitis. However, all these patients develop chronic pancreatitis, rather than SAP with ALI (9, 10). Therefore,

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Section: A Model For Sap-induced Lethal Alimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality

et al. 2013

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“…IL-6 levels are also correlated with symptom severity in acute pancreatitis [36]. Indeed, transgenic overexpression of IL-6 in the pancreas results in a severe inflammatory reaction associated with infiltration of mononuclear cells [37].…”

Section: Il-6 In Acutementioning

confidence: 99%

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

1999

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Inflammation refers to a complex set of mechanisms by which tissues respond to injury and infection. Among the many soluble mediators associated with this process, cytokines are known to be crucial in regulating a variety of cellular and molecular events. Leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and possibly other members of this cytokine family are key mediators in various inflammatory processes such as the acute-phase reaction, tissue damage, and infection. These cytokines can act in both pro-inflammatory and anti-inflammatory ways, depending on a number of variables. We emphasize here recent work utilizing knockout mice, which has highlighted the roles of LIF and IL-6, particularly in interactions between the immune and nervous systems.

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“…Hallazgos similares son los obtenidos por Heresbach (30) y Mayer (18), aunque la mayoría de las publicaciones detectan los valores máxi-mos antes de las 48 horas (31)(32)(33)(34)(35). En cualquier caso, la IL-6 es considerada la más útil clínicamente como marcador de gravedad (35)(36)(37)(38)(39). Algunos estudios sugieren que la asociación de IL-6 y lipasa pudieran ser buenos parámetros de diagnóstico y pronóstico en la práctica clí-nica diaria (34).…”

Section: Discussionunclassified

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

Martín¹,

Saracibar²,

Santa-Maria³

et al. 2008

Rev. esp. enferm. dig.

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A pesar de que en la actualidad poseemos conocimientos más profundos sobre la fisiopatología de la pancreatitis aguda (PA), y que disponemos de mejores medios terapéuticos fundamentalmente a nivel de cuidados intensivos, sin embargo se mantiene una elevada morbili- RESUMENObjetivo: se trata de comparar prospectivamente el comportamiento durante la primera semana del ingreso de los niveles de interleucina-18 (IL-18), y otros parámetros inmunológicos entre pacientes con pancreatitis aguda con y sin criterios de gravedad, así como entre pacientes con y sin desarrollo ulterior de seudoquiste.Pacientes y métodos: se compararon en 36 pacientes con pancreatitis aguda los resultados de sTNF-RI, IL-1Ra, IL-6 e IL-18 los días 1, 2, 3 y 7 desde el ingreso entre pancretitis leve, grave y un grupo control (13 pacientes) con cólico biliar simple, así como entre pacientes con o sin seudoquiste.Resultados: al comparar pancreatitis leve con grave, IL-18 fue significativamente superior sólo el primer día en las pancreatitis graves y los otros parámetros a partir del segundo día de forma mantenida. También en pacientes que desarrollaron seudoquiste, IL-18 estuvo significativamente elevada el primer día.Conclusiones: IL-18 resultó el marcador más precoz de complicaciones y gravedad de la pancreatitis aguda a nivel sistémico y local (seudoquiste).Palabras clave: Interleucina-18. Pancreatitis aguda. Gravedad. Seudoquiste. ABSTRACTObjective: our aim was to prospectively compare the behavior of interleukin 18 (IL-18) levels and other immunological parameters during the first week of hospitalization between acute pancreatitis patients with and without severity criteria, as well as between patients with and without late pseudocyst development.Patients and methods: in 36 patients with acute pancreatitis we compared sTNF-RI, IL-1Ra, IL-6, and IL-18 levels at days 1, 2, 3 and 7 after hospitalization between mild pancreatitis, severe pancreatitis, and a "control" group (13 patients) with uncomplicated biliary colic, as well as between patients with and without pseudocyst.Results: on comparing mild to severe pancreatitis, IL-18 was significantly higher only the first day in severe pancreatitis, while the other parameters were steadily higher after the second day. In patients developing pseudocyst, IL-18 was also noticeably higher the first day.Conclusions: IL-18 appears to be the earliest marker of complications and severity in acute pancreatitis at both the systemic and local level (pseudocyst).

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Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis

Cited by 326 publications

References 11 publications

IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality

IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

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

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