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. 1998 Sep;43(3):408–413. doi: 10.1136/gut.43.3.408

Multisystemic production of interleukin 10 limits the severity of acute pancreatitis in mice

J-L Van Laethem 1, R Eskinazi 1, H Louis 1, F Rickaert 1, P Robberecht 1, J Deviere 1
PMCID: PMC1727255  PMID: 9863488

Abstract

Background—Interleukin 10 (IL-10) decreases the severity of experimental acute pancreatitis. The role of endogenous IL-10 in modulating the course of pancreatitis is currently unknown. 
Aims—To examine the systemic release of IL-10 and its messenger RNA production in the pancreas, liver, and lungs and analyse the effects of IL-10 neutralisation in caerulein induced acute pancreatitis in mice. 
Methods—Acute necrotising pancreatitis was induced by intraperitoneal caerulein. Serum levels of IL-10 and tumour necrosis factor (TNF), and tissue IL-10 and TNF-α gene expression were assessed. After injecting control antibody or after blocking the activity of endogenous IL-10 by a specific monoclonal antibody, the severity of acute pancreatitis was assessed in terms of serum enzyme release, histological changes, and systemic and tissue TNF production. 
Results—In control conditions, serum IL-10 levels increased and correlated with the course of pancreatitis, with a maximal value eight hours after induction. Both IL-10 and TNF-α messengers showed a similar course, and were identified in the pancreas, liver, and lungs. Neutralisation of endogenous IL-10 significantly increased the severity of pancreatitis and associated lung injury as well as serum TNF protein levels (+75%) and pancreatic, pulmonary, and hepatic TNF messenger expression (+33%, +29%, +43%, respectively). 
Conclusions—In this non-lethal model, systemic release of IL-10 correlates with the course of acute pancreatitis. This anti-inflammatory response parallels the release of TNF and both cytokines are produced multisystemically. Endogenous IL-10 controls TNF-α production and plays a protective role in the local and systemic consequences of the disease. 



Keywords: pancreatitis; interleukin 10; tumour necrosis factor α; adult respiratory distress syndrome

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Figure 1 .

Figure 1

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Time course of serum IL-10 levels after induction of pancreatitis (time 0 corresponds to the first caerulein injection). Values are expressed as mean (SD) for each time point: n=8 (2 hours); n=12 (4 hours); n=13 (8 hours); n=15 (15 hours). *p=0.03 (2 hours), p=0.012 (4 hours), p=0.008 (8 hours), compared with time 0. 


Figure 2 .

Figure 2

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Kinetics of the representative expression of IL-10 mRNA in the pancreas during acute pancreatitis (three mice tested at each time point). M, molecular weight marker. 


Figure 3 .

Figure 3

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(A) Representative expression of TNF-α mRNA in the liver during the course of acute pancreatitis. Two positive controls (+LPS) were included showing high expression of TNF-α mRNA in the liver one hour after intraperitoneal injection of 100 µg lipopolysaccharide. (B) Expression of IL-10 mRNA in the pancreas, liver, and lungs at the time of maximal pancreatitic intensity. M, molecular weight marker. C, positive control from the liver (+LPS). 


Figure 4 .

Figure 4

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Kinetics of serum amylase (A) and lipase (B) levels after induction of pancreatitis. Values are mean (SD); n=10 at each time point. *p<0.05, **p<0.01. 


Figure 5 .

Figure 5

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Serum TNF-α levels after pretreatment with anti-IL-10 monoclonal antibody or control monoclonal antibody, four and eight hours after induction of pancreatitis. Values expressed as mean (SD); n=8 in each group; threshold value of detection was 20 pg/ml. *p<0.05, **p<0.01. 


Figure 6 .

Figure 6

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Assessment of TNF-α mRNA during acute pancreatitis. M, molecular weight marker. 


Figure 7 .

Figure 7

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Neutrophil count in the lungs of mice pretreated with anti-IL-10 monoclonal antibody and controls. Results expressed as mean (SD)/high power field (HPF); the numbers of neutrophils were counted in 10 HPF from five lungs in each group. **p<0.001, *p<0.008. 


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