Kupffer cell blockade reduces hepatic and systemic cytokine levels and lung injury in hemorrhagic pancreatitis in rats.
Severe acute pancreatitis (AP) is associated with both the local (pancreatic) release of cytokines and an elevation in their systemic plasma concentrations. This may lead to organ dysfunction and death of the patient. The aims of this study were to investigate the source(s) of systemic cytokine production during experimental AP. Forty-two rats were allocated to five groups (control, sham operation and saline injection, sham operation and gadolinium chloride injection, intraductal sodium-taurocholate infusion and saline injection, or intraductal sodium-taurocholate infusion and gadolinium chloride injection). Blood from the iliac artery, portal vein, and hepatic vein, along with tissue from the pancreas, liver, and lung, were collected. Serum levels of TNFalpha, IL-1beta, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay. Tissue mRNA for IL-1beta and IL-10 was assessed by reverse-transcription polymerase chain reaction. In untreated animals with AP, the lowest serum cytokine levels were found in the portal vein. In the hepatic vein, the levels of TNFalpha, IL-1beta, and IL-6 were higher. The highest serum levels were detected in the systemic circulation. In the gadolinium chloride-treated group, there was no increase in hepatic or systemic cytokine levels and less lung injury was observed. Extrapancreatic cytokine production from both the liver and the lung contributed significantly to systemic levels of TNFalpha, IL-1beta, IL-6, and IL-10 in this experimental model of AP.
Gloor
B
B
Department of Surgery, UCLA School of Medicine, 90095, USA.
Blinman
T A
TA
Rigberg
D A
DA
Todd
K E
KE
Lane
J S
JS
Hines
O J
OJ
Reber
H A
HA
D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000032:analysis* / Q000235:genetics; D005260:Female; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000737:chemistry*; D008168:Lung / Q000473:pathology*; D010195:Pancreatitis / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D012333:RNA, Messenger