NSAIDs do not prevent NTIS but alter thyroid hormone responsiveness in the septic diaphragm.

Non-thyroidal illness syndrome (NTIS) is frequently observed during sepsis and involves alterations in thyroid hormone (TH) metabolism and action, which may contribute to metabolic and muscular dysfunction. The systemic inflammatory response affects TH responsiveness by modulating the expression of deiodinase enzymes, which regulate the activation (DIO1, DIO2) or inactivation (DIO3) of THs. In this context, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may represent a strategy to mitigate NTIS-related alterations and preserve muscle function during sepsis. Sepsis was induced in 4-month-old male C57BL/6 mice by cecal ligation and puncture (CLP). Mice received meropenem (20 mg/kg) with or without the NSAID meloxicam (2 mg/kg; CLPN and CLP, respectively) or underwent sham surgery (Sham). Animals were euthanized 24 h later (CEUA-UFRJ 100/23). Hepatic Dio1 expression was reduced in CLPN compared with Sham and CLP (Sham 1.00±0.20; CLPN 0.20±0.16; CLP 1.02±1.04; p<0.02). Dio3 expression was reduced in CLPN versus Sham (Sham 1.02±0.49; CLPN 0.26±0.21; CLP 0.61±0.24; p<0.01). In contrast, Il1b expression was reduced in the CLPN group, as expected, whereas it was increased in the CLP group (Sham 1.00±0.59; CLPN 0.69±0.54; CLP 5.26±2.58; p<0.01). In the muscular context, Dio2 expression was increased in the diaphragm of CLP animals compared with the CLPN (Sham 1.00±0.70; CLPN 0.59±0.31; CLP 1.94±1.44; p<0.01). Furthermore, expression of the TH receptor, Thra1, was reduced in CLP animals compared with the Sham group (Sham 1.00±0.71; CLPN 0.57±0.48; CLP 0.22±0.19; p=0.04). Our results suggest that NSAID treatment reduces deiodinase expression and preserves Thra1. Reduced Il1b expression further suggests that inflammation control may attenuate NTIS and preserve muscle responsiveness. The tissue-specific deiodinase responses warrant further studies to determine their functional relevance to respiratory muscle function.