title: Mathematical modeling of the circadian dynamics of the neuroendocrine-immune network in experimentally induced arthritis.
abstract: The circadian dynamics of important neuroendocrine-immune mediators have been implicated in progression of rheumatoid arthritis pathophysiology, both clinically as well as in animal models. We present a mathematical model that describes the circadian interactions between mediators of the hypothalamic-pituitary-adrenal (HPA) axis and the proinflammatory cytokines. Model predictions demonstrate that chronically elevated cytokine expression results in the development of adrenal insufficiency and circadian variability in paw edema. Notably, our model also predicts that an increase in mean secretion of corticosterone (CST) after the induction of the disease is accompanied by a decrease in the amplitude of the CST oscillation. Furthermore, alterations in the phase of circadian oscillation of both cytokines and HPA axis mediators are observed. Therefore, by incorporating the circadian interactions between the neuroendocrine-immune mediators, our model is able to simulate important features of rheumatoid arthritis pathophysiology.
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers State University of New Jersey, Piscataway, New Jersey;
authors.forename: R
authors.initials: R
authors.lastname: Rao
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York; and.
authors.forename: D
authors.initials: D
authors.lastname: DuBois
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York; and.
authors.forename: R
authors.initials: R
authors.lastname: Almon
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York;
authors.forename: W J
authors.initials: WJ
authors.lastname: Jusko
authors.affiliation: Department of Chemical and Biochemical Engineering, Rutgers State University of New Jersey, Piscataway, New Jersey; Department of Biomedical Engineering, Rutgers State University of New Jersey, Piscataway, New Jersey yannis@rci.rutgers.edu.
authors.forename: I P
authors.initials: IP
authors.lastname: Androulakis
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D002940:Circadian Rhythm / Q000276:immunology; D003345:Corticosterone / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D016207:Cytokines / Q000276:immunology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008962:Models, Theoretical; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012377:Rodentia
chemical_list: D016207:Cytokines; D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: HPA axis; experimentally induced arthritis; mathematical modeling; neuroendocrine-immune network; proinflammatory cytokines