Inflammation induced by snake venoms optimizes envenomation.

Snake envenomation activates the immune system through permeability-increasing factors that generate an acute vascular inflammatory response by opening large inflammation-activated pores (IAPs) in the microvasculature. These events facilitate the exudation of plasma from blood into body tissues. However we show that IAPs also allow macromolecules, including venom toxins, to flood directly into the bloodstream, even against an outflow of plasma solutes. Such inflammation-facilitated macromolecular absorption (IFMA) acts together with lymphatic absorption and has a physiological role in removing interstitial molecules, as evidenced by our dextran studies. IFMA will function in vascular absorption of interstitial molecules, potentially up to the radius of IAPs, which we determined to be 21 nm (95% confidence interval (CI) 18-24 nm). This absorption depends on factors, including the interstitial-vascular concentration gradient, the reflection coefficient of each molecule and microvascular pressure. Molecules absorbed will include snake venom toxins and various cellular breakdown products that arise during processes such as the inflammatory phase of wound healing. Most, if not all, venom toxins will be absorbed, as these typically have a hydrodynamic radius (r