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Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system.
Peptides 2014; 61:56-60P

Abstract

The nociceptin receptor (NOP) and its ligand nociceptin/orphanin FQ (N/OFQ) have been shown to exert a modulatory effect on immune cells during sepsis. We evaluated the suitability of an experimental lipopolysaccharide (LPS)-induced sepsis model for studying changes in the nociceptin system. C57BL/6 mice BALB/c mice and Wistar rats were inoculated with different doses of LPS with or without a nociceptin receptor antagonist (UFP-101 or SB-612111). In C57BL/6 mice LPS 0.85 mg/kg injection produced no septic response, whereas 1.2mg/kg produced a profound response within 5h. In BALB/c mice, LPS 4 mg/kg produced no response, whereas 7 mg/kg resulted in a profound response within 24h. In Wistar rats LPS 15 mg/kg caused no septic response in 6/10 animals, whereas 25mg/kg resulted in marked lethargy before 24h. Splenic interleukin-1β mRNA in BALB/c mice, and serum TNF-α concentrations in Wistar rats increased after LPS injection in a dose-dependent manner, but were undetectable in control animals, indicating that LPS had stimulated an inflammatory reaction. IL-1β and TNF-α concentrations in LPS-treated animals were unaffected by administration of a NOP antagonist. Similarly NOP antagonists had no effect on survival or expression of mRNA for NOP or ppN/OFQ (the N/OFQ precursor) in a variety of tissues. In these animal models, the dose-response curve for LPS was too steep to allow use in survival studies and no changes in the N/OFQ system occurred within 24h. We conclude that LPS-inoculation in rodents is an unsuitable model for studying possible changes in the NOP-N/OFQ system in sepsis.

Authors+Show Affiliations

Department of Cardiovascular Sciences, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom. Electronic address: rct17@le.ac.uk.Department of Cardiovascular Sciences, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom. Electronic address: mfb11@student.le.ac.uk.Department of Infection, Inflammation and Immunity, University of Leicester, Medical Sciences Building, University Road, Leicester LE1 9HN, United Kingdom. Electronic address: cms13@le.ac.uk.Department of Cardiovascular Sciences, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom. Electronic address: dgl3@le.ac.uk.Department of Cardiovascular Sciences, Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom. Electronic address: jt23@le.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25161013

Citation

Thomas, Roisin C., et al. "Exploring LPS-induced Sepsis in Rats and Mice as a Model to Study Potential Protective Effects of the Nociceptin/orphanin FQ System." Peptides, vol. 61, 2014, pp. 56-60.
Thomas RC, Bath MF, Stover CM, et al. Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system. Peptides. 2014;61:56-60.
Thomas, R. C., Bath, M. F., Stover, C. M., Lambert, D. G., & Thompson, J. P. (2014). Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system. Peptides, 61, pp. 56-60. doi:10.1016/j.peptides.2014.08.009.
Thomas RC, et al. Exploring LPS-induced Sepsis in Rats and Mice as a Model to Study Potential Protective Effects of the Nociceptin/orphanin FQ System. Peptides. 2014;61:56-60. PubMed PMID: 25161013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system. AU - Thomas,Roisin C, AU - Bath,Michael F, AU - Stover,Cordula M, AU - Lambert,David G, AU - Thompson,Jonathan P, Y1 - 2014/08/23/ PY - 2014/07/02/received PY - 2014/08/14/revised PY - 2014/08/14/accepted PY - 2014/8/28/entrez PY - 2014/8/28/pubmed PY - 2015/7/30/medline KW - Nociceptin KW - Nociceptin receptor KW - Nociceptin/Orphanin FQ KW - SB-612111 KW - Sepsis KW - UFP-101 SP - 56 EP - 60 JF - Peptides JO - Peptides VL - 61 N2 - The nociceptin receptor (NOP) and its ligand nociceptin/orphanin FQ (N/OFQ) have been shown to exert a modulatory effect on immune cells during sepsis. We evaluated the suitability of an experimental lipopolysaccharide (LPS)-induced sepsis model for studying changes in the nociceptin system. C57BL/6 mice BALB/c mice and Wistar rats were inoculated with different doses of LPS with or without a nociceptin receptor antagonist (UFP-101 or SB-612111). In C57BL/6 mice LPS 0.85 mg/kg injection produced no septic response, whereas 1.2mg/kg produced a profound response within 5h. In BALB/c mice, LPS 4 mg/kg produced no response, whereas 7 mg/kg resulted in a profound response within 24h. In Wistar rats LPS 15 mg/kg caused no septic response in 6/10 animals, whereas 25mg/kg resulted in marked lethargy before 24h. Splenic interleukin-1β mRNA in BALB/c mice, and serum TNF-α concentrations in Wistar rats increased after LPS injection in a dose-dependent manner, but were undetectable in control animals, indicating that LPS had stimulated an inflammatory reaction. IL-1β and TNF-α concentrations in LPS-treated animals were unaffected by administration of a NOP antagonist. Similarly NOP antagonists had no effect on survival or expression of mRNA for NOP or ppN/OFQ (the N/OFQ precursor) in a variety of tissues. In these animal models, the dose-response curve for LPS was too steep to allow use in survival studies and no changes in the N/OFQ system occurred within 24h. We conclude that LPS-inoculation in rodents is an unsuitable model for studying possible changes in the NOP-N/OFQ system in sepsis. SN - 1873-5169 UR - https://www.unboundmedicine.com/medline/citation/25161013/Exploring_LPS_induced_sepsis_in_rats_and_mice_as_a_model_to_study_potential_protective_effects_of_the_nociceptin/orphanin_FQ_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(14)00252-6 DB - PRIME DP - Unbound Medicine ER -