title: Mathematical modeling in necrotizing enterocolitis--a new look at an ongoing problem.
abstract: Necrotizing enterocolitis (NEC) is the most common and lethal disease that affects the gastrointestinal (GI) tract of the premature infant. The etiology of NEC remains undefined. The only consistent epidemiological precursors for NEC are prematurity and enteral alimentation. Various inflammatory mediators, including tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, platelet-activating factor (PAF), and nitric oxide (NO) have been implicated in the pathogenesis of NEC, but the kinetics and role of these agents are ill-defined. Currently, there are no biomarker predictors of NEC risk and severity. Sera or tissue from early time points in the development of the disease may help delineate early inflammatory events that predispose an individual to NEC, thus providing an interventional opportunity. We suggest that the lack of diagnostic and therapeutic modalities for NEC are due to the absence of a systems view of the disease, which in turn is hindered by a lack of sensitive physiological measurements that predict perturbations in the intestinal tissue compartment and an inability to reliably test serial samples for the presence of inflammatory mediators in small volumes and in a high-throughput manner. Computational modeling is a useful tool in the study of complex systems such as the inflammatory process. Computation models provide an "existence proof" for a given mechanism, uncover subtle inconsistencies between the underlying hypotheses and quantitative data, and force one to ask how much is known. We suggest that a properly validated and calibrated mathematical model of inflammation and its pathologic consequences in NEC will be useful for predicting the physiologic and biologic response in infants suffering from the disease.
authors.affiliation: Department of Pediatric Surgery, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA. jupperman@chla.usc.edu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Upperman
authors.forename: Victoria
authors.initials: V
authors.lastname: Camerini
authors.forename: Brian
authors.initials: B
authors.lastname: Lugo
authors.forename: Ivan
authors.initials: I
authors.lastname: Yotov
authors.forename: Joshua
authors.initials: J
authors.lastname: Sullivan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rubin
authors.forename: Joshua
authors.initials: J
authors.lastname: Rubin
authors.forename: Giles
authors.initials: G
authors.lastname: Clermont
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.forename: G Bard
authors.initials: GB
authors.lastname: Ermentrout
authors.forename: Henri R
authors.initials: HR
authors.lastname: Ford
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D008954:Models, Biological
chemical_list: D015415:Biomarkers