 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
15 January 1998 | Volume 128 Issue 2 | Pages 127-137
Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
Author and Article Information
An edited summary of a Clinical Staff Conference held on 13 March 1996 at the National Institutes of Health, Bethesda, Maryland.
ARTICLE
The Pathophysiologic Roles of Interleukin-6 in Human Disease
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Wilder RL. Interleukin-6 in autoimmune and inflammatory diseases, pp 130-132. In: Papanicolaou DA, moderator. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998; 128:127-137.
For definitions of terms used in the text, see Glossary at end of text.
Requests for Reprints: Dimitris A. Papanicolaou, MD, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, MD 20892-1862
Current Author Addresses: Dr. Papanicolaou: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, MD 20892-1862.
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  A. Sebba Tocilizumab: The first interleukin-6-receptor inhibitor Am. J. Health Syst. Pharm., August 1, 2008; 65(15): 1413 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. M. Nater, L. S. Youngblood, J. F. Jones, E. R. Unger, A. H. Miller, W. C. Reeves, and C. Heim Alterations in Diurnal Salivary Cortisol Rhythm in a Population-Based Sample of Cases With Chronic Fatigue Syndrome Psychosom Med, April 1, 2008; 70(3): 298 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Lim, K. S. Thomas, W. A. Bardwell, and J. E. Dimsdale Which Measures of Obesity Are Related to Depressive Symptoms and in Whom? Psychosomatics, February 1, 2008; 49(1): 23 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S-S. Lee, S. Singh, L. Magder, and M. Petri Predictors of high sensitivity C-reactive protein levels in patients with systemic lupus erythematosus Lupus, February 1, 2008; 17(2): 114 - 123. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Akalin, O. Alatas, and O. Colak Relation of plasma homocysteine levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetic patients Eur. J. Endocrinol., January 1, 2008; 158(1): 47 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Reilly, V. Poylin, M. Menconi, A. Onderdonk, S. Bengmark, and P.-O. Hasselgren Probiotics potentiate IL-6 production in IL-1beta-treated Caco-2 cells through a heat shock-dependent mechanism Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1169 - R1179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Jankord, J. R. Turk, J. C. Schadt, J. Casati, V. K. Ganjam, E. M. Price, D. H. Keisler, and M. H. Laughlin Sex Difference in Link between Interleukin-6 and Stress Endocrinology, August 1, 2007; 148(8): 3758 - 3764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-F. O'Connor, S. J. Motivala, E. M. Valladares, R. Olmstead, and M. R. Irwin Sex differences in monocyte expression of IL-6: role of autonomic mechanisms Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R145 - R151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Finotto, T. Eigenbrod, R. Karwot, I. Boross, A. Doganci, H. Ito, N. Nishimoto, K. Yoshizaki, T. Kishimoto, S. Rose-John, et al. Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells Int. Immunol., June 1, 2007; 19(6): 685 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. C. van Helvoort, Y. F. Heijdra, R. C. C. de Boer, A. Swinkels, H. M. H. Thijs, and P. N. R. Dekhuijzen Six-Minute Walking-Induced Systemic Inflammation and Oxidative Stress in Muscle-Wasted COPD Patients Chest, February 1, 2007; 131(2): 439 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Su, Z. Wang, Y. Cai, M. Remmelink, and J.-L. Vincent Beneficial Effects of Ethyl Pyruvate in Septic Shock From Peritonitis Arch Surg, February 1, 2007; 142(2): 166 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zoccali, G. Tripepi, and F. Mallamaci Dissecting Inflammation in ESRD: Do Cytokines and C-Reactive Protein Have a Complementary Prognostic Value for Mortality in Dialysis Patients? J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S169 - S173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. von Kanel, J. E. Dimsdale, P. J. Mills, S. Ancoli-Israel, T. L. Patterson, B. T. Mausbach, and I. Grant Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and d-dimer. J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2006; 61(9): 963 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Diez Roux, N. Ranjit, L. Powell, S. Jackson, T. T. Lewis, S. Shea, and C. Wu Psychosocial factors and coronary calcium in adults without clinical cardiovascular disease. Ann Intern Med, June 6, 2006; 144(11): 822 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lecube, C. Hernandez, J. Genesca, and R. Simo Glucose Abnormalities in Patients with Hepatitis C Virus Infection: Epidemiology and pathogenesis Diabetes Care, May 1, 2006; 29(5): 1140 - 1149. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ishida, F. Kimura, M. Imamaki, A. Ishida, H. Shimura, H. Kohno, M. Sakurai, and M. Miyazaki Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting. Eur. J. Cardiothorac. Surg., April 1, 2006; 29(4): 501 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Trichopoulos, T. Psaltopoulou, P. Orfanos, A. Trichopoulou, and P. Boffetta Plasma C-reactive protein and risk of cancer: a prospective study from Greece. Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 381 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Friedman, M. S. Hayney, G. D. Love, H. L. Urry, M. A. Rosenkranz, R. J. Davidson, B. H. Singer, and C. D. Ryff Social relationships, sleep quality, and interleukin-6 in aging women PNAS, December 20, 2005; 102(51): 18757 - 18762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-p. Zhao, P. Deng, H.-g. Huang, Z.-m. Xu, H.-y. Dai, S.-c. Hong, J. Yang, and H.-n. Zhou Expression of COX-2 mRNA in Peripheral Blood Monocytes from Patients with Acute Myocardial Infarction and Its Significance Clin. Chem., November 1, 2005; 51(11): 2170 - 2173. [Full Text] [PDF]
|
|
|
|
|
|
G. E. Miller, N. Rohleder, C. Stetler, and C. Kirschbaum Clinical Depression and Regulation of the Inflammatory Response During Acute Stress Psychosom Med, September 1, 2005; 67(5): 679 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Bhattacharyya, K Kaushal, D J Tymms, and J R E Davis Steroid withdrawal syndrome after successful treatment of Cushing's syndrome: a reminder Eur. J. Endocrinol., August 1, 2005; 153(2): 207 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. V. Doering, D. K. Moser, W. Lemankiewicz, C. Luper, and S. Khan Depression, Healing, and Recovery From Coronary Artery Bypass Surgery Am. J. Crit. Care., July 1, 2005; 14(4): 316 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Margeli, K. Skenderi, M. Tsironi, E. Hantzi, A.-L. Matalas, C. Vrettou, E. Kanavakis, G. Chrousos, and I. Papassotiriou Dramatic Elevations of Interleukin-6 and Acute-Phase Reactants in Athletes Participating in the Ultradistance Foot Race Spartathlon: Severe Systemic Inflammation and Lipid and Lipoprotein Changes in Protracted Exercise J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3914 - 3918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, R. F. Schwabe, T. DeVries-Seimon, P. M. Yao, M.-C. Gerbod-Giannone, A. R. Tall, R. J. Davis, R. Flavell, D. A. Brenner, and I. Tabas Free Cholesterol-loaded Macrophages Are an Abundant Source of Tumor Necrosis Factor-{alpha} and Interleukin-6: MODEL OF NF-{kappa}B- AND MAP KINASE-DEPENDENT INFLAMMATION IN ADVANCED ATHEROSCLEROSIS J. Biol. Chem., June 10, 2005; 280(23): 21763 - 21772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Alesci, P. E. Martinez, S. Kelkar, I. Ilias, D. S. Ronsaville, S. J. Listwak, A. R. Ayala, J. Licinio, H. K. Gold, M. A. Kling, et al. Major Depression Is Associated with Significant Diurnal Elevations in Plasma Interleukin-6 Levels, a Shift of Its Circadian Rhythm, and Loss of Physiological Complexity in Its Secretion: Clinical Implications J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2522 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamamoto, K. Takeshita, T. Kojima, J. Takamatsu, and H. Saito Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly Cardiovasc Res, May 1, 2005; 66(2): 276 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Lim, S. Hong, R. Nelesen, and J. E. Dimsdale The Association of Obesity, Cytokine Levels, and Depressive Symptoms With Diverse Measures of Fatigue in Healthy Subjects Arch Intern Med, April 25, 2005; 165(8): 910 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rega, C. Kaun, T.W. Weiss, S. Demyanets, G. Zorn, S.P. Kastl, S. Steiner, D. Seidinger, C.W. Kopp, M. Frey, et al. Inflammatory Cytokines Interleukin-6 and Oncostatin M Induce Plasminogen Activator Inhibitor-1 in Human Adipose Tissue Circulation, April 19, 2005; 111(15): 1938 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Gordon, R. J. O'Keefe, E. M. Schwarz, R. N. Rosier, and J. E. Puzas Nuclear Factor-{kappa}B-Dependent Mechanisms in Breast Cancer Cells Regulate Tumor Burden and Osteolysis in Bone Cancer Res., April 15, 2005; 65(8): 3209 - 3217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Memoli, G. Grandaliano, M. Soccio, L. Postiglione, B. Guida, V. Bisesti, P. Esposito, A. Procino, D. Marrone, A. Michael, et al. In Vivo Modulation of Soluble "Antagonistic" IL-6 Receptor Synthesis and Release in ESRD J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1099 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Schaefer, J. V. Fahey, J. A. Wright, and C. R. Wira Innate Immunity in the Human Female Reproductive Tract: Antiviral Response of Uterine Epithelial Cells to the TLR3 Agonist Poly(I:C) J. Immunol., January 15, 2005; 174(2): 992 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Huber, C. Grimm, S. Jirecek, R. Zeillinger, K. Heim, P. Husslein, and L. Hefler An lnterleukin-6 Gene Promoter Polymorphism and Unexplained Late Intrauterine Fetal Death: A Multicenter Study Reproductive Sciences, January 1, 2005; 12(1): 33 - 36. [Abstract] [PDF]
|
|
|
|
|
|
K. M. Choi, K. W. Lee, S. G. Kim, N. H. Kim, C. G. Park, H. S. Seo, D. J. Oh, D. S. Choi, and S. H. Baik Inflammation, Insulin Resistance, and Glucose Intolerance in Acute Myocardial Infarction Patients without a Previous Diagnosis of Diabetes Mellitus J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 175 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Hamid, S. A. Urhammer, D. P. Jensen, C. Glumer, K. Borch-Johnsen, T. Jorgensen, T. Hansen, and O. Pedersen Variation in the Interleukin-6 Receptor Gene Associates With Type 2 Diabetes in Danish Whites Diabetes, December 1, 2004; 53(12): 3342 - 3345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Silverman, A. H. Miller, C. A. Biron, and B. D. Pearce Characterization of an Interleukin-6- and Adrenocorticotropin-Dependent, Immune-to-Adrenal Pathway during Viral Infection Endocrinology, August 1, 2004; 145(8): 3580 - 3589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Kovacs, T. P. Plackett, and P. L. Witte Estrogen replacement, aging, and cell-mediated immunity after injury J. Leukoc. Biol., July 1, 2004; 76(1): 36 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Melamed, A. Shirom, S. Toker, S. Berliner, and I. Shapira Association of Fear of Terror With Low-Grade Inflammation Among Apparently Healthy Employed Adults Psychosom Med, July 1, 2004; 66(4): 484 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Kip, O. C. Marroquin, D. E. Kelley, B. D. Johnson, S. F. Kelsey, L. J. Shaw, W. J. Rogers, and S. E. Reis Clinical Importance of Obesity Versus the Metabolic Syndrome in Cardiovascular Risk in Women: A Report From the Women's Ischemia Syndrome Evaluation (WISE) Study Circulation, February 17, 2004; 109(6): 706 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Volpato, M. Pahor, L. Ferrucci, E. M. Simonsick, J. M. Guralnik, S. B. Kritchevsky, R. Fellin, and T. B. Harris Relationship of Alcohol Intake With Inflammatory Markers and Plasminogen Activator Inhibitior-1 in Well-Functioning Older Adults: The Health, Aging, and Body Composition Study Circulation, February 10, 2004; 109(5): 607 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kandere-Grzybowska, R. Letourneau, D. Kempuraj, J. Donelan, S. Poplawski, W. Boucher, A. Athanassiou, and T. C. Theoharides IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells J. Immunol., November 1, 2003; 171(9): 4830 - 4836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Glaser, T. F. Robles, J. Sheridan, W. B. Malarkey, and J. K. Kiecolt-Glaser Mild Depressive Symptoms Are Associated With Amplified and Prolonged Inflammatory Responses After Influenza Virus Vaccination in Older Adults Arch Gen Psychiatry, October 1, 2003; 60(10): 1009 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yang, X. Han, T. Uchiyama, S. K. Watkins, A. Yaguchi, R. L. Delude, and M. P. Fink IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice Am J Physiol Gastrointest Liver Physiol, August 8, 2003; 285(3): G621 - G629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Kiecolt-Glaser, K. J. Preacher, R. C. MacCallum, C. Atkinson, W. B. Malarkey, and R. Glaser Chronic stress and age-related increases in the proinflammatory cytokine IL-6 PNAS, July 22, 2003; 100(15): 9090 - 9095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Roldan, F. Marin, A. D Blann, A. Garcia, P. Marco, F. Sogorb, and G. Y.H Lip Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation Eur. Heart J., July 2, 2003; 24(14): 1373 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Huang, X. Pang, K. Karalis, and T. C. Theoharides Stress-induced interleukin-6 release in mice is mast cell-dependent and more pronounced in Apolipoprotein E knockout mice Cardiovasc Res, July 1, 2003; 59(1): 241 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pecoits-Filho, B. Lindholm, J. Axelsson, and P. Stenvinkel Update on interleukin-6 and its role in chronic renal failure Nephrol. Dial. Transplant., June 1, 2003; 18(6): 1042 - 1045. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Madhotra and I.T. Gilmore Recent developments in the treatment of alcoholic hepatitis QJM, June 1, 2003; 96(6): 391 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Cappola, Q.-L. Xue, L. Ferrucci, J. M. Guralnik, S. Volpato, and L. P. Fried Insulin-Like Growth Factor I and Interleukin-6 Contribute Synergistically to Disability and Mortality in Older Women J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2019 - 2025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Vgontzas, M. Zoumakis, E. O. Bixler, H.-M. Lin, P. Prolo, A. Vela-Bueno, A. Kales, and G. P. Chrousos Impaired Nighttime Sleep in Healthy Old Versus Young Adults Is Associated with Elevated Plasma Interleukin-6 and Cortisol Levels: Physiologic and Therapeutic Implications J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2087 - 2095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Fernandez-Real, M. Broch, J. Vendrell, and W. Ricart Insulin Resistance, Inflammation, and Serum Fatty Acid Composition Diabetes Care, May 1, 2003; 26(5): 1362 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Luo, D. D. Hershko, B. W. Robb, C. J. Wray, and P.-O. Hasselgren IL-1beta stimulates IL-6 production in cultured skeletal muscle cells through activation of MAP kinase signaling pathway and NF-kappa B Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2003; 284(5): R1249 - R1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Salmenpera, S. Hamalainen, M. Hukkanen, and E. Kankuri Interferon-gamma induces C/EBPbeta expression and activity through MEK/ERK and p38 in T84 colon epithelial cells Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1133 - C1139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Halpern, M. B. Sholar, J. Glowacki, N. K. Mello, J. H. Mendelson, and A. J. Siegel Diminished Interleukin-6 Response to Proinflammatory Challenge in Men and Women after Intravenous Cocaine Administration J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1188 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Beishuizen and L. G. Thijs Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis Innate Immunity, February 1, 2003; 9(1): 3 - 24. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Unfried, S. Bocskor, G. Endler, F. Nagele, J.C. Huber, and C.B. Tempfer A polymorphism of the interleukin-6 gene promoter and idiopathic recurrent miscarriage Hum. Reprod., February 1, 2003; 18(2): 267 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Redwine, J. Dang, M. Hall, and M. Irwin Disordered Sleep, Nocturnal Cytokines, and Immunity in Alcoholics Psychosom Med, January 1, 2003; 65(1): 75 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Hershko, B. W. Robb, G. Luo, and P.-O. Hasselgren Multiple transcription factors regulating the IL-6 gene are activated by cAMP in cultured Caco-2 cells Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2002; 283(5): R1140 - R1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
Article
