PMID- 18469453
OWN - NLM
STAT- MEDLINE
DCOM- 20080722
LR  - 20131121
IS  - 1590-8577 (Electronic)
IS  - 1590-8577 (Linking)
VI  - 9
IP  - 3
DP  - 2008 May 8
TI  - Ritonavir and disulfiram may be synergistic in lowering active interleukin-18 
      levels in acute pancreatitis, and thereby hasten recovery.
PG  - 350-3
AB  - Interleukin-18 (IL-18) is one of the mediators of both pancreas damage and 
      systemic complications like hypotension and multi-organ dysfunction during acute 
      pancreatitis. IL-18 is generated intracellularly from pro-IL-18 by caspase-1 
      mediated proteolysis. Active caspase-1 itself is generated intracellularly by the 
      action of the inflammasome, autocatalysis and other stimuli. The anti-retroviral 
      drug ritonavir inhibits conversion of inactive pro-caspase-1 to active caspase-1. 
      Since ritonavir is well tolerated in short-term use it may therefore prove useful 
      in treating acute pancreatitis by lowering caspase-1 mediated IL-18 formation and 
      the many inflammatory mediators downstream from that. The alcoholism treatment 
      drug disulfiram has been in continuous use since the 1950s. It likewise has a low 
      risk profile. Disulfiram inhibits several human proteases, among them caspase-1. 
      Given the current morbidity and mortality of pancreatitis, research should be 
      directed to ritonavir and disulfiram as treatment options for illnesses like 
      pancreatitis where excessive IL-18 contributes to pathology. The first clinically 
      used angiotensin converting enzyme inhibitor, captopril, has shown potent 
      caspase-1 inhibiting activity as well and should be investigated in rodent models 
      of human pancreatitis.
FAU - Kast, Richard Eric
AU  - Kast RE
LA  - eng
PT  - Letter
PT  - Review
DEP - 20080508
PL  - England
TA  - JOP
JT  - JOP : Journal of the pancreas
JID - 101091810
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-18)
RN  - 9G64RSX1XD (Captopril)
RN  - O3J8G9O825 (Ritonavir)
RN  - TR3MLJ1UAI (Disulfiram)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Captopril/pharmacology
MH  - Caspase Inhibitors
MH  - Disulfiram/administration & dosage/*pharmacology
MH  - Drug Synergism
MH  - Enzyme Inhibitors/administration & dosage/pharmacology
MH  - Humans
MH  - Interleukin-18/*blood/metabolism/physiology
MH  - Models, Biological
MH  - Pancreatitis/blood/*drug therapy/etiology
MH  - Remission Induction
MH  - Ritonavir/administration & dosage/*pharmacology
MH  - Time Factors
RF  - 19
EDAT- 2008/05/13 09:00
MHDA- 2008/07/23 09:00
CRDT- 2008/05/13 09:00
PHST- 2008/05/13 09:00 [pubmed]
PHST- 2008/07/23 09:00 [medline]
PHST- 2008/05/13 09:00 [entrez]
AID - v09i03a17 [pii]
PST - epublish
SO  - JOP. 2008 May 8;9(3):350-3.