Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice
Abstract Background Symptoms associated with acute pancreatitis can be debilitating, and treatment remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of acute pancreatitis. Methods...
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-021-01827-0 |
| _version_ | 1818937688498110464 |
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| author | Rajasa Randhi Melissa Damon Kirsty J. Dixon |
| author_facet | Rajasa Randhi Melissa Damon Kirsty J. Dixon |
| author_sort | Rajasa Randhi |
| collection | DOAJ |
| description | Abstract Background Symptoms associated with acute pancreatitis can be debilitating, and treatment remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of acute pancreatitis. Methods Acute pancreatitis was induced in adult male C57Bl/6J mice by administering cerulein (8 injections of 50 µg/kg I.P., spaced an hour apart), with XPro1595 (10 mg/kg, S.C.) or vehicle being administered approximately 18 h after the last injection. Serum was collected 6 or 18 h after the last cerulein injection, pancreatic tissue was collected 2 and 7 days post-induction, and brain hippocampal tissue was collected at 7 days post-induction. The animal’s pain level was assessed 3, 5 and 7 days post-induction. Results The induction of acute pancreatitis promoted a strong increase in serum amylase levels, which had receded back to baseline levels by the next morning. XPro1595 treatment began after amylase levels had subsided at 18 h, and prevented pancreatic immune cell infiltration, that subsequently prevented tissue disruption and acinar cell death. These improvements in pathology were associated with a significant reduction in mechanical hypersensitivity (neuropathic pain). XPro1595 treatment also prevented an increase in hippocampal astrocyte reactivity, that may be associated with the prevention of neuropathic pain in this mouse model. Conclusion Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of cerulein-induced pancreatitis in mice, which provides support of its use in patients with pancreatitis. |
| first_indexed | 2024-12-20T05:55:56Z |
| format | Article |
| id | doaj.art-ecd3117c6d8240cd955d1dbecc73b8bf |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-12-20T05:55:56Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-ecd3117c6d8240cd955d1dbecc73b8bf2022-12-21T19:51:02ZengBMCBMC Gastroenterology1471-230X2021-05-0121111010.1186/s12876-021-01827-0Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in miceRajasa Randhi0Melissa Damon1Kirsty J. Dixon2Department of Surgery, Virginia Commonwealth UniversityDepartment of Surgery, Virginia Commonwealth UniversityDepartment of Surgery, Virginia Commonwealth UniversityAbstract Background Symptoms associated with acute pancreatitis can be debilitating, and treatment remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of acute pancreatitis. Methods Acute pancreatitis was induced in adult male C57Bl/6J mice by administering cerulein (8 injections of 50 µg/kg I.P., spaced an hour apart), with XPro1595 (10 mg/kg, S.C.) or vehicle being administered approximately 18 h after the last injection. Serum was collected 6 or 18 h after the last cerulein injection, pancreatic tissue was collected 2 and 7 days post-induction, and brain hippocampal tissue was collected at 7 days post-induction. The animal’s pain level was assessed 3, 5 and 7 days post-induction. Results The induction of acute pancreatitis promoted a strong increase in serum amylase levels, which had receded back to baseline levels by the next morning. XPro1595 treatment began after amylase levels had subsided at 18 h, and prevented pancreatic immune cell infiltration, that subsequently prevented tissue disruption and acinar cell death. These improvements in pathology were associated with a significant reduction in mechanical hypersensitivity (neuropathic pain). XPro1595 treatment also prevented an increase in hippocampal astrocyte reactivity, that may be associated with the prevention of neuropathic pain in this mouse model. Conclusion Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of cerulein-induced pancreatitis in mice, which provides support of its use in patients with pancreatitis.https://doi.org/10.1186/s12876-021-01827-0Acute pancreatitisCeruleinMiceInflammationCytokinesTNF |
| spellingShingle | Rajasa Randhi Melissa Damon Kirsty J. Dixon Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice BMC Gastroenterology Acute pancreatitis Cerulein Mice Inflammation Cytokines TNF |
| title | Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice |
| title_full | Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice |
| title_fullStr | Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice |
| title_full_unstemmed | Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice |
| title_short | Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice |
| title_sort | selective inhibition of soluble tnf using xpro1595 relieves pain and attenuates cerulein induced pathology in mice |
| topic | Acute pancreatitis Cerulein Mice Inflammation Cytokines TNF |
| url | https://doi.org/10.1186/s12876-021-01827-0 |
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