Mañana, JUEVES, 24 DE ABRIL, el sistema se apagará debido a tareas habituales de mantenimiento a partir de las 9 de la mañana. Lamentamos las molestias.
A system dynamics model to predict the human monocyte response to endotoxins
Author
Álvarez, Enrique; Toledano, Víctor; Morilla, Fernando; Hernández-Jiménez, Enrique; Cubillos-Zapata, Carolina; Varela-Serrano, Aníbal; Casas-Martín, José; Avendaño-Ortiz, José; Aguirre, Luis A.; Arnalich Fernández, Francisco; Maroun-Eid, Charbel; Martín-Quirós, Alejandro; Quintana Díaz, Manuel; López-Collazo, EduardoEntity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)Publisher
Frontiers MediaDate
2017-08-03Citation
10.3389/fimmu.2017.00915
Frontiers in Immunology 8 (2017): 915
ISSN
1664-3224DOI
10.3389/fimmu.2017.00915Funded by
This work was supported by grants from the “Instituto de Salud Carlos III” (ISCiii), “Fondo de Investigación Sanitaria” (FIS), and Fondos FEDER (PI14/01234, PIE15/00065) to EL-C. EA work contract is supported by the Torres Quevedo program from “Ministerio de Economía y Competitividad” (SPTQ1300X006175XV0). VT work contract is supported by the “Ministerio de Economía y Competitividad” (PTA2013-8265-I)Project
Gobierno de España. PI14/01234; Gobierno de España. PIE15/00065; Gobierno de España. PTA2013-8265-IEditor's Version
https://doi.org/10.3389/fimmu.2017.00915Subjects
Bacterial lipopolysaccharide; Endotoxin tolerance; Inflammation; Mathematical model; Monocytes; MedicinaRights
© 2017 Álvarez, Toledano, Morilla, Hernández-Jiménez, Cubillos-Zapata, Varela-Serrano, Casas-Martín, Avendaño-Ortiz, Aguirre, Arnalich, Maroun-Eid, Martín-Quirós, Quintana Díaz and López-CollazoAbstract
System dynamics is a powerful tool that allows modeling of complex and highly networked systems such as those found in the human immune system. We have developed a model that reproduces how the exposure of human monocytes to lipopolysaccharides (LPSs) induces an inflammatory state characterized by high production of tumor necrosis factor alpha (TNFα), which is rapidly modulated to enter into a tolerant state, known as endotoxin tolerance (ET). The model contains two subsystems with a total of six states, seven flows, two auxiliary variables, and 14 parameters that interact through six differential and nine algebraic equations. The parameters were estimated and optimized to obtain a model that fits the experimental data obtained from human monocytes treated with various LPS doses. In contrast to publications on other animal models, stimulation of human monocytes with super-low-dose LPSs did not alter the response to a second LPSs challenge, neither inducing ET, nor enhancing the inflammatory response. Moreover, the model confirms the low production of TNFα and increased levels of C-C motif ligand 2 when monocytes exhibit a tolerant state similar to that of patients with sepsis. At present, the model can help us better understand the ET response and might offer new insights on sepsis diagnostics and prognosis by examining the monocyte response to endotoxins in patients with sepsis
Files in this item
Google Scholar:Álvarez, Enrique
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Toledano, Víctor
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Morilla, Fernando
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Hernández-Jiménez, Enrique
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Cubillos-Zapata, Carolina
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Varela-Serrano, Aníbal
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Casas-Martín, José
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Avendaño-Ortiz, José
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Aguirre, Luis A.
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Arnalich Fernández, Francisco
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Maroun-Eid, Charbel
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Martín-Quirós, Alejandro
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Quintana Díaz, Manuel
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López-Collazo, Eduardo
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