title: The role of the hypothalamic-pituitary-adrenal axis in modulating seasonal changes in immunity.
abstract: Seasonal changes in environmental conditions are accompanied by significant adjustment of multiple biological processes. In temperate regions, the day fraction, or photoperiod, is a robust environmental cue that synchronizes seasonal variations in neuroendocrine and metabolic function. In this work, we propose a semimechanistic mathematical model that considers the influence of seasonal photoperiod changes as well as cellular and molecular adaptations to investigate the seasonality of immune function. Our model predicts that the circadian rhythms of cortisol, our proinflammatory mediator, and its receptor exhibit seasonal differences in amplitude and phase, oscillating at higher amplitudes in the winter season with peak times occurring later in the day. Furthermore, the reduced photoperiod of winter coupled with seasonal alterations in physiological activity induces a more exacerbated immune response to acute stress, simulated in our studies as the administration of an acute dose of endotoxin. Our findings are therefore in accordance with experimental data that reflect the predominance of a proinflammatory state during the winter months. These changes in circadian rhythm dynamics may play a significant role in the seasonality of disease incidence and regulate the diurnal and seasonal variation of disease symptom severity.
authors.affiliation: Biomedical Engineering Department, Rutgers University, Piscataway, New Jersey.
authors.forename: Kamau
authors.initials: K
authors.lastname: Pierre
authors.affiliation: Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.
authors.forename: Naomi
authors.initials: N
authors.lastname: Schlesinger
authors.affiliation: Biomedical Engineering Department, Rutgers University, Piscataway, New Jersey; Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, New Jersey; and Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey yannis@rci.rutgers.edu.
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Androulakis
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology; D002940:Circadian Rhythm / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000276:immunology; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology*; D007109:Immunity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008962:Models, Theoretical; D017440:Photoperiod; D010913:Pituitary-Adrenal System / Q000276:immunology*; D012621:Seasons
chemical_list: D006854:Hydrocortisone
keywords: circadian; cortisol; immunity; photoperiod; seasonal