Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B

Katia Fettucciari,1 Alessandro Fruganti,2 Andrea Marchegiani,2 Stefano Brancorsini,1 Pierfrancesco Marconi,1 Gabrio Bassotti3,4 1Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy; 2School of Biosciences and Veterinary Medicine, University of Camerino, Macerata...

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Autores principales:	Fettucciari K, Fruganti A, Marchegiani A, Brancorsini S, Marconi P, Bassotti G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	clostridioides difficile toxin b proinflammatory cytokines tnf-alpha ifn-gamma systemic effects Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/015ab6e143b34f98b5a148c321491e45
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spelling	oai:doaj.org-article:015ab6e143b34f98b5a148c321491e452021-12-02T15:14:37ZProinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B1178-7031https://doaj.org/article/015ab6e143b34f98b5a148c321491e452021-01-01T00:00:00Zhttps://www.dovepress.com/proinflammatory-cytokines-possible-accomplices-for-the-systemic-effect-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Katia Fettucciari,1 Alessandro Fruganti,2 Andrea Marchegiani,2 Stefano Brancorsini,1 Pierfrancesco Marconi,1 Gabrio Bassotti3,4 1Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy; 2School of Biosciences and Veterinary Medicine, University of Camerino, Macerata, Italy; 3Gastroenterology, Hepatology & Digestive Endoscopy Section, Department of Medicine, University of Perugia Medical School, Perugia, Italy; 4Gastroenterology & Hepatology Unit, Santa Maria della Misericordia Hospital, Perugia, ItalyCorrespondence: Katia FettucciariDepartment of Experimental Medicine, University of Perugia Medical School, Piazza Lucio Severi 1, Edificio B IV Piano, Sant’Andrea delle Fratte, Perugia 06132, ItalyTel +39755858124Email katia.fettucciari@unipg.itAbstract: Clostridioides difficile infection (CDI) has a serious impact on the healthcare system, and most of its pathogenic effects are mainly due to the activity of toxins A and B (TcdA and TcdB, respectively). The molecular mechanisms of their cytotoxic activity are well known, especially in the colon, where the infection occurs and normally remains localized. However, the mechanisms causing toxic effects on various systemic organs (extraintestinal manifestations) with frequent lethal outcomes in some patients affected by CDI are still poorly understood. Few studies are available that demonstrate low serum levels of Tcds in both experimental animal models and patients with CDI. Until now, it has remained unclear how low levels of circulating Tcds could lead to serious toxic effects. On the basis of our previous in vitro studies, in which the proinflammatory cytokines TNF-alpha and IFN-gamma strongly potentiated the toxic activity of low doses of TcdB, we hypothesize that the presence of both TcdB in the circulation and a systemic proinflammatory cytokine storm may be responsible for the selective severe effects of TcdB in some patients. This may occur in patients with severe CDI and systemic Tcds, in whom proinflammatory cytokines such as TNF-alpha and IFN-gamma reach a significant concentration in the circulation. This hypothesis could identify therapeutic interventions based on the reduction or neutralization of the indirect toxic action of these cytokines.Keywords: Clostridioides difficile, toxin B, proinflammatory cytokines, TNF-alpha, IFN-gamma, systemic effectsFettucciari KFruganti AMarchegiani ABrancorsini SMarconi PBassotti GDove Medical Pressarticleclostridioides difficiletoxin bproinflammatory cytokinestnf-alphaifn-gammasystemic effectsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 57-62 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	clostridioides difficile toxin b proinflammatory cytokines tnf-alpha ifn-gamma systemic effects Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	clostridioides difficile toxin b proinflammatory cytokines tnf-alpha ifn-gamma systemic effects Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Fettucciari K Fruganti A Marchegiani A Brancorsini S Marconi P Bassotti G Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B
description	Katia Fettucciari,1 Alessandro Fruganti,2 Andrea Marchegiani,2 Stefano Brancorsini,1 Pierfrancesco Marconi,1 Gabrio Bassotti3,4 1Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy; 2School of Biosciences and Veterinary Medicine, University of Camerino, Macerata, Italy; 3Gastroenterology, Hepatology & Digestive Endoscopy Section, Department of Medicine, University of Perugia Medical School, Perugia, Italy; 4Gastroenterology & Hepatology Unit, Santa Maria della Misericordia Hospital, Perugia, ItalyCorrespondence: Katia FettucciariDepartment of Experimental Medicine, University of Perugia Medical School, Piazza Lucio Severi 1, Edificio B IV Piano, Sant’Andrea delle Fratte, Perugia 06132, ItalyTel +39755858124Email katia.fettucciari@unipg.itAbstract: Clostridioides difficile infection (CDI) has a serious impact on the healthcare system, and most of its pathogenic effects are mainly due to the activity of toxins A and B (TcdA and TcdB, respectively). The molecular mechanisms of their cytotoxic activity are well known, especially in the colon, where the infection occurs and normally remains localized. However, the mechanisms causing toxic effects on various systemic organs (extraintestinal manifestations) with frequent lethal outcomes in some patients affected by CDI are still poorly understood. Few studies are available that demonstrate low serum levels of Tcds in both experimental animal models and patients with CDI. Until now, it has remained unclear how low levels of circulating Tcds could lead to serious toxic effects. On the basis of our previous in vitro studies, in which the proinflammatory cytokines TNF-alpha and IFN-gamma strongly potentiated the toxic activity of low doses of TcdB, we hypothesize that the presence of both TcdB in the circulation and a systemic proinflammatory cytokine storm may be responsible for the selective severe effects of TcdB in some patients. This may occur in patients with severe CDI and systemic Tcds, in whom proinflammatory cytokines such as TNF-alpha and IFN-gamma reach a significant concentration in the circulation. This hypothesis could identify therapeutic interventions based on the reduction or neutralization of the indirect toxic action of these cytokines.Keywords: Clostridioides difficile, toxin B, proinflammatory cytokines, TNF-alpha, IFN-gamma, systemic effects
format	article
author	Fettucciari K Fruganti A Marchegiani A Brancorsini S Marconi P Bassotti G
author_facet	Fettucciari K Fruganti A Marchegiani A Brancorsini S Marconi P Bassotti G
author_sort	Fettucciari K
title	Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B
title_short	Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B
title_full	Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B
title_fullStr	Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B
title_full_unstemmed	Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B
title_sort	proinflammatory cytokines: possible accomplices for the systemic effects of clostridioides difficile toxin b
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/015ab6e143b34f98b5a148c321491e45
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Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Clostridioides difficile Toxin B

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