Fig 6. In silico clinical trials suggest little efficacy for corticosteroids or DAMP inhibitors.

Simulations are shown at t = 700 h. We varied both the dose and timing of corticosteroid administration, simulated as an injection into the bloodstream, under (A) alternating pressure and (B) 40% initial injury conditions. When inflammatory cells were neutralized early enough but pressure continued, overall damage decreased, but ulceration was not prevented. Without continuous pressure cycles, the earliest dose of steroids was successful in stemming ulcer formation, but later applications did not. We then varied both the dose and timing of administration of a neutralizing antibody to HMGB1, simulated as a topical cream applied to the entire field. This targeted approach had (C) no apparent effect during simulations with alternating pressure, but (D) was able to slow ulcer formation after a 40% initial injury without pressure.