Table A1.

Mediators Represented in the CBIABM, Their Functions in the Model, and Associated References.

Mediator	Modeled Functions and References
Pathogen/Damage-Associated Molecular Patterns (P/DAMPS)	Produced when cells die by some other means than apoptosis (pyroptosis or necrosis). Persists in the presence of non-apoptosis dead cells until phagocytosed by macrophages. Functions a chemoattractant for macrophages, shifts macrophages to proinflammatory phenotype, primes inflammasomes [24,25]. Added to by “metabolic byproduct” (“Met-By”) as simulated extracellular DNA from cellular damage from metabolic stress. Diffuse at 0.1, Evaporate at 0.90.
Reactive Oxygen Species (ROS)	Produced during PMN respiratory burst, damages epithelial cells [29]. Diffuse at 0.1, Evaporate at 0.90.
Platelet-Activating Factor (PAF)	Made by activated endothelial cells, functions as chemotaxis and adhesion activation/recruitment signal for PMNs [28,29]. Diffuse at 0.1, Evaporate at 0.90.
Tumor Necrosis Factor (TNF)	Produced by proinflammatory macrophages, functions to activate the inflammasome in macrophages, activates endothelium, consumed by epithelial cells [6,7,8,29]. Diffuse at 0.2, Evaporate at 0.99.
Interleukin-1 (IL-1)	Produced by inflammasome priming and activation in macrophages, primarily released at pyroptosis, produced by PMNs, functions to activate endothelium and shift macrophages to proinflammatory phenotype, along with TNF stimulates infected epithelial cells to produce IL-6 [3,4,6,7,44]. Consumed by macrophages. Diffuses at 0.2, Evaporates at 0.99.
Interleukin-18 (IL-18)	Produced by infected epithelial cells. Produced by inflammasome priming and activation in macrophages and primarily released at pyroptosis, facilitate NK cells to produce IFNg (in conjunction with T1IFN and IL-12), consumed by NK cells [3,4,6,7,8,50]. Diffuses at 0.2, Evaporates at 0.99.
Interleukin-6 (IL-6)	Produced by proinflammatory macrophages, dendritic cells, and infected epithelial cells [51,52], diffuses at 0.2, evaporates at 0.99.
Interleukin-8 (IL-8)	Produced by proinflammatory macrophages, functions as chemotactic compound for PMNs [29]. Diffuses at 0.3, evaporates at 0.99.
Interleukin-10 (IL-10)	Produced by both pro- and anti-inflammatory macrophages, function is to shift balance of macrophages from proinflammatory to anti-inflammatory phenotypes [53,54]. Consumed by macrophages. Diffuses at 0.2, evaporates at 0.99.
Interleukin-12 (IL-12)	Produced by dendritic cells and proinflammatory macrophages, function to facilitate NK cell production of IFNg (in conjunction with IL-18 and T1IFN) [55,56]. Consumed by NK cells. Diffuses at 0.2, Evaporates at 0.99.
Type 1 Interferons (T1IFN)	Produced by infected epithelial cells and NK cells, functions as chemotactic compound for NK cells, dendritic cells, and macrophages, facilitates production of IFNg by NK cells (in conjunction with IL-12 and IL-18), induces production of IL-12, IFNg, and (in conjunction with IL-1) IL6, has antiviral effect by reducing viral replication in infected epithelial cells, constitutively produced in bats, only induced in humans, enhances apoptosis in response to viral infection [3,4,57,58,59]. Consumed by macrophages and dendritic cells. Diffuses at 0.1, Evaporates at 0.99.
Interferon-gamma (IFNg)	Produced by NK cells, proinflammatory macrophages, dendritic cells, functions to shift macrophages toward proinflammatory phenotype [58,60,61]. Consumed by macrophages. Diffuses at 0.2, evaporates at 0.99.