Irene T Lee1, Alexandria Atuahene1, Hale Ergin Egritag1,2, Ling Wang1,2, Michael Donovan3, Christoph Buettner1,2, Eliza B Geer1,4. 1. Division of Endocrinology, Metabolism and Diabetes, Icahn School of Medicine at Mount Sinai, New York, New York. 2. Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 3. Division of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York. 4. Division of Endocrinology, Department of Medicine, and Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York.
Abstract
CONTEXT: Although glucocorticoids (GCs) have potent anti-inflammatory actions, patients with hypercortisolism due to Cushing disease (CD) have increased circulating proinflammatory cytokines that may contribute to their insulin resistance and cardiovascular disease. The mechanisms and tissues that account for the increased systemic inflammation in patients with CD are unknown. OBJECTIVE: To determine whether chronic endogenous GC exposure due to CD is associated with adipose tissue (AT) inflammation in humans. DESIGN, SETTING, PARTICIPANTS: Abdominal subcutaneous AT samples from 10 patients with active CD and 10 age-, sex-, and body mass index‒matched healthy subjects were assessed for macrophage infiltration and mRNA expression of proinflammatory cytokines. MAIN OUTCOME MEASURE: Using immunohistochemistry, AT samples were analyzed for the expression of vimentin, caspase, CD3, CD4, CD8, CD11c, CD20, CD31, CD56, CD68, and CD163. Quantitative PCR was used to assess the mRNA gene expression of arginase, CD11b, CD68, EMR-1, IL-6, IL-10, MCP-1, and TNF-α. RESULTS: Immunohistochemistry revealed higher mean percentage infiltration of CD68+ macrophages and CD4+ T lymphocytes, increased mean area of CD11c+ M1 macrophages, higher number of CD11c+ crownlike structures, and decreased vimentin in the AT of patients with active CD compared with controls. PCR revealed no differences in mRNA expression of any analyzed markers in patients with CD. CONCLUSIONS: Chronic exposure to GCs due to CD increases the presence of AT macrophages, a hallmark of AT inflammation. Hence, AT inflammation may be the source of the systemic inflammation seen in CD, which in turn may contribute to obesity, insulin resistance, and cardiovascular disease in these patients.
CONTEXT: Although glucocorticoids (GCs) have potent anti-inflammatory actions, patients with hypercortisolism due to Cushing disease (CD) have increased circulating proinflammatory cytokines that may contribute to their insulin resistance and cardiovascular disease. The mechanisms and tissues that account for the increased systemic inflammation in patients with CD are unknown. OBJECTIVE: To determine whether chronic endogenous GC exposure due to CD is associated with adipose tissue (AT) inflammation in humans. DESIGN, SETTING, PARTICIPANTS: Abdominal subcutaneous AT samples from 10 patients with active CD and 10 age-, sex-, and body mass index‒matched healthy subjects were assessed for macrophage infiltration and mRNA expression of proinflammatory cytokines. MAIN OUTCOME MEASURE: Using immunohistochemistry, AT samples were analyzed for the expression of vimentin, caspase, CD3, CD4, CD8, CD11c, CD20, CD31, CD56, CD68, and CD163. Quantitative PCR was used to assess the mRNA gene expression of arginase, CD11b, CD68, EMR-1, IL-6, IL-10, MCP-1, and TNF-α. RESULTS: Immunohistochemistry revealed higher mean percentage infiltration of CD68+ macrophages and CD4+ T lymphocytes, increased mean area of CD11c+ M1 macrophages, higher number of CD11c+ crownlike structures, and decreased vimentin in the AT of patients with active CD compared with controls. PCR revealed no differences in mRNA expression of any analyzed markers in patients with CD. CONCLUSIONS: Chronic exposure to GCs due to CD increases the presence of AT macrophages, a hallmark of AT inflammation. Hence, AT inflammation may be the source of the systemic inflammation seen in CD, which in turn may contribute to obesity, insulin resistance, and cardiovascular disease in these patients.
Authors: T E Scholzen; C Sunderkötter; D-H Kalden; T Brzoska; M Fastrich; T Fisbeck; C A Armstrong; J C Ansel; T A Luger Journal: Endocrinology Date: 2003-01 Impact factor: 4.736
Authors: Stuart P Weisberg; Daniel McCann; Manisha Desai; Michael Rosenbaum; Rudolph L Leibel; Anthony W Ferrante Journal: J Clin Invest Date: 2003-12 Impact factor: 14.808
Authors: Miguel Tavares Pereira; Isabelle Martin; Hubert Rehrauer; Mariusz P Kowalewski; Felicitas S Boretti; Nadja S Sieber-Ruckstuhl Journal: Vet Sci Date: 2022-05-25