Abstract / Summary
Abstract Hypothyroidism decreases the basal metabolic rate. Using three models of peritonitis, intraperitoneal LPS plus Zymosan challenge, cecal slurry-induced intraperitoneal infection, and cecal ligation and puncture, we demonstrate that hypothyroid mice show enhanced survival compared to euthyroid mice. Hypothyroid mice show lower energy expenditure, reduced CO2/O2 exchange, and decreased movements prior to treatment. However, they maintain greater physiological stability following LPS plus zymosan challenge and are capable of recovering homeostatic values. In contrast, euthyroid mice, which begin with higher energy expenditure and CO2/O2 exchange rates, show a rapid sharp decline and severe hypoglycemia after treatment, not observed in hypothyroid mice. Two days postchallenge, hypothyroid mice exhibit decreased levels of circulating proinflammatory cytokines and tissue-specific IL-6 in liver, lung, and kidney. Consequently, hypothyroid mice exhibit significantly lower circulating levels of systemic, hepatic, renal, and pulmonary tissue-damage markers. These findings correlate with a decrease in ferroptosis and an attenuation of hepatic phospholipid peroxidation. In the early hours following peritoneal cecal slurry-induced infection, hypothyroid mice display a significant decrease in peritoneal levels of proinflammatory cytokines and circulating neutrophil counts. Crucially, both groups show comparable intraperitoneal bacterial proliferation, similar counts of both large and small peritoneal macrophages, with an analogous phagocytic capacity and similar disappearance rate. In conclusion, hypothyroidism increases tolerance to polymicrobial peritoneal infection, specifically by mitigating inflammation and disease severity while leaving bacterial dynamics unaffected.