1. Date of download: 7/7/2016 From: The Pathophysiologic Roles of Interleukin-6 in Human Disease Ann Intern Med. 1998;128(2):127-137. doi:10.7326/0003-4819-128-2-199801150-00009 Transcriptional regulation of the interleukin-6 (IL-6) promoter.Glucocorticoids inhibit transcription of interleukin-6 through interaction of the ligand-activated glucocorticoid receptor (GR) with the Re1A subunit of transcription factor NF-κB. Estrogens suppress transcription (slashed arrows) of interleukin-6 through formation of heteromeric estrogen receptor (ER)-C/EBPbeta and estrogen receptor-NF-κB complexes. AP-1 = AP-1 site; CREB = cyclic adenosine 5′-monophosphate-response element binding site; C/EBP = C/EBP binding site; NF-κB = NF-κB binding site. The triangle represents glucocorticoid; the rhombus represents estrogen. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

2. Date of download: 7/7/2016 From: The Pathophysiologic Roles of Interleukin-6 in Human Disease Ann Intern Med. 1998;128(2):127-137. doi:10.7326/0003-4819-128-2-199801150-00009 Pleiotropy of interleukin-6 (IL-6) action.Binding of circulating interleukin-6 to the soluble interleukin-6 receptor (sIL-6R) may activate gp130 subunits present on cells that lack the specific interleukin-6 receptor, probably those that are activated by the leptin receptor (OB-R), leukemia inhibitory factor receptor (LIF-R) (for leukemia inhibitory factor, oncostatin-M, ciliary neurotrophic factor, and cardiotropin-1), and oncostatin-M receptor (OMR) (for oncostatin-M). Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

3. Date of download: 7/7/2016 From: The Pathophysiologic Roles of Interleukin-6 in Human Disease Ann Intern Med. 1998;128(2):127-137. doi:10.7326/0003-4819-128-2-199801150-00009 Regulation of the secretion and endocrine actions of interleukin-6 (IL-6).Interleukin-6 production is stimulated by tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). Interleukin-6, in turn, inhibits further production of tumor necrosis factor-α and interleukin-1. Catecholamines stimulate interleukin-6 production, whereas glucocorticoids, estrogens, and androgens suppress it. Interleukin-6 acutely stimulates the corticotropin-releasing hormone (CRH) neuron, which leads to increased secretion of adrenocorticotropin hormone (ACTH) and cortisol. It also stimulates the secretion of growth hormone (GH) and arginine vasopressin (AVP) (at high levels) but suppresses thyroid-stimulating hormone (TSH) secretion and levels of circulating lipids. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

4. Date of download: 7/7/2016 From: The Pathophysiologic Roles of Interleukin-6 in Human Disease Ann Intern Med. 1998;128(2):127-137. doi:10.7326/0003-4819-128-2-199801150-00009 Changes in circulating hormones and interleukin-6 with aging in men and women. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians