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Zierke et al. Rare Dis Orphan Drugs J 2023;2:10 https://dx.doi.org/10.20517/rdodj.2022.17 Page 7 of 10

While serine protease inhibitors have attenuated disease severity by reduction of both pancreatic and extra-
[73]
pancreatic injury in experimental models and prophylactic administration of the serine protease inhibitor
[74]
gabexate mesylate has reduced the rate of post-ERCP pancreatitis in high-risk patients , data regarding
usefulness of NSP inhibitors in treating acute pancreatitis are limited and restricted to preclinical models.

Sivelestat, a specific inhibitor of NE, protected against pancreatic and lung injury in rats that had undergone
[75]
caerulein- or taurocholate-induced acute pancreatitis . Additive effects were achieved when treatment was
combined with antioxidant resveratrol . Lex032, an inhibitor of elastase and cathepsin G, ameliorated
[76]
microcirculatory function in ischemia/reperfusion-induced acute pancreatitis by the preservation of
capillary perfusion, absence of interleukin-6 increase, and preservation of mean arterial pressure during
reperfusion time, indicating usefulness in preventing pancreatic tissue damage from
[77]
ischemia/reperfusion . Despite promising results in preclinical investigations, the effectiveness of NSP
modulation in clinical use remains to be validated.

CONCLUSION
Despite advances in understanding the pathogenesis of acute pancreatitis, the precise cellular and
subcellular mechanisms of the early disease phase are not entirely understood. Neutrophils are recruited to
inflamed sites and drive inflammatory reactions by several processes, including the activation of NSPs.
Several animal models suggest a favorable effect on acute pancreatitis when neutrophil elastase is inhibited.
Recent data support the pro-inflammatory role of NSPs in acute pancreatitis; however, their pathogenic
functions in autoimmune and hereditary pancreatitis, two rarer forms of pancreatitis, still need to be
clarified.

DECLARATIONS
Authors’ contributions
Literature research and writing: Zierke L, Gischke M, Tran QT, Aghdassi AA
Final approval of the draft: Zierke L, Gischke M, Tran QT, Aghdassi AA

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was funded by the Deutsche Forschungsgemeinschaft (DFG AG 203/4-1).

Conflicts of interest
All authors declare that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2023.