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Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine

Administration of recombinant human IL-18 binding protein (rhIL-18BP), a natural antagonist of IL-18, significantly increased mouse survival after lethal doses of irradiation. To further understand the roles of IL-18BP in radiation mitigation, we studied the pharmacokinetic (PK) parameters of rhIL-1...

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Autores principales: Cui, Wanchang, Hull, Lisa, Zizzo, Alex, Wang, Li, Lin, Bin, Zhai, Min, Xiao, Mang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863660/
https://www.ncbi.nlm.nih.gov/pubmed/36668761
http://dx.doi.org/10.3390/toxics11010035
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author Cui, Wanchang
Hull, Lisa
Zizzo, Alex
Wang, Li
Lin, Bin
Zhai, Min
Xiao, Mang
author_facet Cui, Wanchang
Hull, Lisa
Zizzo, Alex
Wang, Li
Lin, Bin
Zhai, Min
Xiao, Mang
author_sort Cui, Wanchang
collection PubMed
description Administration of recombinant human IL-18 binding protein (rhIL-18BP), a natural antagonist of IL-18, significantly increased mouse survival after lethal doses of irradiation. To further understand the roles of IL-18BP in radiation mitigation, we studied the pharmacokinetic (PK) parameters of rhIL-18BP, and the serum and intestinal cytokine changes in CD2F1 mice treated with vehicle or rhIL-18BP after 9.0 Gy total body irradiation (TBI). For the PK study, non-compartmental pharmacokinetic analysis was performed using PKsolver. Serum and intestine specimens were collected to measure 44-cytokine levels. Principal component analysis showed a clear separation of the non-irradiated samples from the irradiated samples; and partial separation with or without rhIL-18BP treatment. Cytokine clusters that were significantly correlated in the serum or intestine, respectively were identified. On the individual cytokine levels, serum and intestinal cytokines that were significantly changed by irradiation and rhIL-18BP treatment were identified. Finally, cytokines that were significantly correlated between their serum and intestinal levels were identified. The current study established the PK parameters of rhIL-18BP in mice, identified significantly changed cytokines in mouse serum and intestine after radiation exposure and rhIL-18BP treatment. Current data provide critical insights into IL-18BP’s mechanism of action as a radiation mitigator.
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spelling pubmed-98636602023-01-22 Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine Cui, Wanchang Hull, Lisa Zizzo, Alex Wang, Li Lin, Bin Zhai, Min Xiao, Mang Toxics Article Administration of recombinant human IL-18 binding protein (rhIL-18BP), a natural antagonist of IL-18, significantly increased mouse survival after lethal doses of irradiation. To further understand the roles of IL-18BP in radiation mitigation, we studied the pharmacokinetic (PK) parameters of rhIL-18BP, and the serum and intestinal cytokine changes in CD2F1 mice treated with vehicle or rhIL-18BP after 9.0 Gy total body irradiation (TBI). For the PK study, non-compartmental pharmacokinetic analysis was performed using PKsolver. Serum and intestine specimens were collected to measure 44-cytokine levels. Principal component analysis showed a clear separation of the non-irradiated samples from the irradiated samples; and partial separation with or without rhIL-18BP treatment. Cytokine clusters that were significantly correlated in the serum or intestine, respectively were identified. On the individual cytokine levels, serum and intestinal cytokines that were significantly changed by irradiation and rhIL-18BP treatment were identified. Finally, cytokines that were significantly correlated between their serum and intestinal levels were identified. The current study established the PK parameters of rhIL-18BP in mice, identified significantly changed cytokines in mouse serum and intestine after radiation exposure and rhIL-18BP treatment. Current data provide critical insights into IL-18BP’s mechanism of action as a radiation mitigator. MDPI 2022-12-30 /pmc/articles/PMC9863660/ /pubmed/36668761 http://dx.doi.org/10.3390/toxics11010035 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cui, Wanchang
Hull, Lisa
Zizzo, Alex
Wang, Li
Lin, Bin
Zhai, Min
Xiao, Mang
Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine
title Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine
title_full Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine
title_fullStr Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine
title_full_unstemmed Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine
title_short Pharmacokinetic Study of rhIL-18BP and Its Effect on Radiation-Induced Cytokine Changes in Mouse Serum and Intestine
title_sort pharmacokinetic study of rhil-18bp and its effect on radiation-induced cytokine changes in mouse serum and intestine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863660/
https://www.ncbi.nlm.nih.gov/pubmed/36668761
http://dx.doi.org/10.3390/toxics11010035
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