Iodine Redistribution During Trauma, Sepsis, and Hibernation: An Evolutionarily Conserved Response to Severe Stress

Abstract

Objective: We performed these studies to learn how iodine in the form of free iodide behaves during stress. Design: Prospective observational trial using samples obtained from human trauma patients and retrospective observational study using remnant samples from human sepsis patients and arctic ground squirrels. Preclinical interventional study using hind-limb ischemia and reperfusion injury in mice. Setting: Level I trauma center emergency room and ICU and animal research laboratories. Subjects: Adult human sepsis and trauma patients, wild-caught adult arctic ground squirrels, and sexually mature laboratory mice. Interventions: Ischemia and reperfusion injury was induced in mice by temporary application of tourniquet to one hind-limb. Iodide was administered IV just prior to reperfusion. Measurements and Main Results: Free iodide was measured using ion chromatography. Relative to iodide in plasma from normal donors, iodide was increased 17-fold in plasma from trauma patients and 26-fold in plasma from sepsis patients. In arctic ground squirrels, iodide increases over three-fold during hibernation. And during ischemia/reperfusion injury in mice, iodide accumulates in ischemic tissue and reduces both local and systemic tissue damage. Conclusions: Iodide redistributes during stress and improves outcome after injury. Essential functions of iodide may have contributed to its evolutionary selection and be useful as a therapeutic intervention for human patients.

Challenging molecular dogmas in human sepsis using mathematical reasoning

“…The switching to a dormancy response to cope with energy availability for cells and tissues must also be mechanistically related to changes in homeostasis setpoints. 64 , 65 These mechanisms of extreme homeostatic regulation may help provide molecular answers for how a life‐threatening organ dysfunction is caused by a dysregulated host response to infection. Energetic demands are high in neonates and children, especially in periods of active growth, and this may contribute a key molecular determinant for the type of immune host response.…”

Elevated levels of iodide promote peroxidase-mediated protein iodination and inhibit protein chlorination

“…Together these data suggest that peroxidase-mediated generation of HOI, and formation of iodinated species, may be relevant in individuals with acute or chronic inflammation, in those with high dietary iodine/iodide/iodinated compound consumption, or following exposure to treatments that elevate I⁻ levels. Data indicate that deliberate elevation of I⁻ is protective in humans in cases of radiation exposure (where oral I⁻ tablets are employed to prevent radioactive I⁻ accumulation), to prevent ischemicreperfusion injury [12][13][14], as a treatment for COVID and other viral diseases (povidone-iodine [71] or I⁻ salts [72]) and sepsis [73].…”