Inflammatory rather than infectious insults play a role in exocrine tissue damage in a mouse model for coxsackievirus B4-induced pancreatitis.
Infection with coxsackievirus B4 (CVB4) may result in an acute severe necrotizing pancreatitis that mostly remains restricted to the acini of the exocrine parenchyma. The mechanisms responsible for this tissue damage, however, remain poorly understood. We here report that COAM, a polyanionic carboxylic acid, provides marked protection against CVB4-induced pancreatitis in a mouse model. Despite the fact that COAM largely reduced disease severity, as detected by serum amylase and lipase levels as well as histologically, titres of replicating CVB4 in the pancreas were virtually unaffected. COAM treatment diminished the infection-associated MMP-9 levels and also resulted in a decreased influx of neutrophils into the infected pancreas. Moreover, we demonstrate that titres of replicating virus in the pancreas did not directly correlate with the severity of disease. In conclusion, our data suggest that immunopathological effects, rather than direct virus-induced destruction, are responsible for the damage to acinar tissue in CVB4-induced pancreatitis.
De Palma
Armando M
AM
Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, University of Leuven, Belgium.
Thibaut
Hendrik J
HJ
Li
Sandra
S
Van Aelst
Ilse
I
Dillen
Chris
C
Swinnen
Melissa
M
Verbeken
Erik
E
Neyts
Johan
J
Opdenakker
Ghislain
G
D000688:Amylose / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003384:Coxsackievirus Infections / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000187:drug effects / Q000302:isolation & purification* / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D010179:Pancreas / Q000201:enzymology / Q000821:virology; D019283:Pancreatitis, Acute Necrotizing / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
C002668:oxyamylose; D000688:Amylose; D020780:Matrix Metalloproteinase 9