The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By ∼12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10–deficient mice. These findings suggest that CRF2-4 is essential for IL-10–mediated effects and is a subunit of the IL-10 receptor.
Leptin, the product of the ob gene, is a hormone secreted by fat cells which is primarily involved in the regulation of body weight. We have generated a leptin immunoadhesin (leptin-IgG) which was more potent than leptin alone at reducing body weight and food intake when injected into ob/ob mice. This molecule was used to identify high affinity binding sites on human embryonic 293 kidney cells and subsequently to isolate a cDNA encoding the leptin receptor from this cell line by expression cloning. This receptor corresponds to the short form of the recently isolated leptin receptor. Analysis of the expression pattern of the two forms of receptor by Northern blot, in situ hybridization and quantitative PCR showed that the receptor is expressed in most tissues but that the long form is prevalent in the hypothalamus.
Objective: We have previously observed thyroid dysfunction, i.e. atypical thyroiditis (painless thyrotoxicosis associated to non-thyroidal illness syndrome), in patients with severe-acute-respiratory-syndrome-coronavirus-2 disease (Covid-19). This study aimed to analyse the evolution of thyroid dysfunction over time.
Methods: 183 consecutive patients hospitalised for severe Covid-19 without known thyroid history were studied at hospital admission (baseline). Survivors were offered 12-month longitudinal follow-up including assessment of thyroid function, autoantibodies and ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive of thyroiditis (focal-hypoechogenicity) also underwent thyroid 99mTc or 123I uptake scan.
Results: At baseline, after excluding from TSH analysis 63 out of 183 (34%) Covid-19 patients commenced on steroids before hospitalisation, 12 (10%) showed atypical thyroiditis. Follow-up of 75 patients showed normalisation of thyroid function and inflammatory markers, and no increased prevalence of detectable thyroid autoantibodies. Baseline US (available in 65 patients) showed focal-hypoechogenicity in 28% patients, of whom 82% had reduced thyroid 99mTc/123I uptake. The presence of focal-hypoechogenicity was associated with baseline low TSH (p=0.034), high FT4 (p=0.018) and high IL-6 (p=0.016). Focal-hypoechogenicity persisted after 6 and 12 months in 87% and 50% patients, respectively, but reduced in size. After 9 months thyroid 99mTc/123I uptake partially recovered from baseline (+28%), but was still reduced in 67% patients.
Conclusions: Severe Covid-19 induces mild transient thyroid dysfunction correlating with disease severity. Focal-hypoechogenicity, associated with baseline high FT4, IL-6 and low TSH, does not seem to be related to thyroid autoimmunity and may persist after one year although decreasing in size. Long-term consequences seem unlikely.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.