Scientist Science & Technology Ctr, HIll's Pet Nutrition Topeka, Kansas, United States
Abstract: Background- Feline hyperthyroidism is characterized by increased production of tetra-iodothyronine (T4) and triiodothyronine (T3) and decreased levels of thyroid stimulating hormone.
Hypothesis- Inflammation, including increased cytokine levels, contributes to the pathogenesis of feline hyperthyroidism.
Animals- Cats clinically diagnosed as having hyperthyroidism by a veterinarian (n = 10, 12.1-18.9yr). Circulating fT4 was significantly higher in hyperthyroid cats (p< 0.05). Control cats showed no signs of hyperthyroidism clinically (n = 10, 10.9-18.6yr).
Methods- RNA was isolated from thyroid tissue collected from cats housed in the Hill’s colony at the natural end-of-life after living full lives. Gene expression was investigated using NanoString nCounter® and analysis performed using nSolver software. Histopathological analysis was performed on hematoxylin and eosin stained slides.
Results– Suppressor of cytokine signaling 1 (SOCS1) was significantly upregulated when compared to controls. There was a significant decrease in Janus Kinase 1 (JAK1) and a decrease in Signal Transducer and Activator of Transcription 1 (STAT1) (ns), IL7R (p< 0.05) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (ns). An increase in SOCS1 and a decrease in the above signaling molecules may affect the production and maintenance of T regulatory cells, potentially leading to autoimmune disorders. There was a significant increase in CXCL14, a pro-inflammatory chemokine and chemoattractant for monocytes and dendritic cells, in hyperthyroid cats. Histopathology from thyroid tissue showed increased follicular cells and evidence of colloid reabsorption in cats with hyperthyroidism compared to controls.
Conclusions and Clinical Importance- These biomarkers represent important targets for reducing inflammation-associated signaling pathways in hyperthyroidism.
