Wilson DM 3rd, Cookson MR, Van Den Bosch L, Zetterberg H, Holtzman DM, Dewachter I (2023) Hallmarks of neurodegenerative diseases. Cell 186:693–714

Article  CAS  PubMed  Google Scholar 

Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, Bohr VA (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15:565–581

Article  PubMed  Google Scholar 

Stephenson J, Nutma E, van der Valk P, Amor S (2018) Inflammation in CNS neurodegenerative diseases. Immunology 154:204–219

Article  CAS  PubMed  PubMed Central  Google Scholar 

Erta M, Quintana A, Hidalgo J (2012) Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 8:1254–1266

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hirano TYK, Harada H (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73–76

Article  CAS  PubMed  Google Scholar 

Somers W, Stahl M, Seehra JS (1997) 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J 16:989–997

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luan D, Dadpey B, Zaid J, Bridge-Comer PE, DeLuca JH, Xia W, Castle J, Reilly SM (2023) Adipocyte-secreted IL-6 sensitizes macrophages to IL-4 signaling. Diabetes 72:367–374

Article  CAS  PubMed  Google Scholar 

Nara H, Watanabe R (2021) Anti-inflammatory effect of muscle-derived interleukin-6 and its involvement in lipid metabolism. Int J Mol Sci 22(18):9889

Article  CAS  PubMed  PubMed Central  Google Scholar 

Said EA, Al-Reesi I, Al-Shizawi N, Jaju S, Al-Balushi MS, Koh CY, Al-Jabri AA, Jeyaseelan L (2021) Defining IL-6 levels in healthy individuals: a meta-analysis. J Med Virol 93:3915–3924

Article  CAS  PubMed  Google Scholar 

Wei J, Xu H, Davies JL, Hemmings GP (1992) Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci 51:1953–1956

Article  CAS  PubMed  Google Scholar 

Tyrrell DJ, Blin MG, Song J, Wood SC, Zhang M, Beard DA, Goldstein DR (2020) Age-associated mitochondrial dysfunction accelerates atherogenesis. Circ Res 126:298–314

Article  CAS  PubMed  Google Scholar 

Alanazi AZ, Clark MA (2019) Angiotensin III induces JAK2/STAT3 leading to IL-6 production in rat vascular smooth muscle cells. Int J Mol Sci 20(22):5551

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu JF, Chi MC, Lin CY, Lee CW, Chang TM, Han CK, Huang YL, Fong YC, Chen HT, Tang CH (2021) PM2.5 facilitates IL-6 production in human osteoarthritis synovial fibroblasts via ASK1 activation. J Cell Physiol 236:2205–2213

Article  CAS  PubMed  Google Scholar 

Russell FD, Visagie JC, Noll JL (2022) Secretion of IL-6 by fibroblasts exposed to Australian honeys involves lipopolysaccharide and is independent of floral source. Sci Rep 12:16628

Article  PubMed  PubMed Central  Google Scholar 

Choi H, Kim K, Han J, Choi H, Jin SH, Lee EK, Shin DW, Lee TR, Lee AY, Noh M (2012) Kojic acid-induced IL-6 production in human keratinocytes plays a role in its anti-melanogenic activity in skin. J Dermatol Sci 66:207–215

Article  CAS  PubMed  Google Scholar 

Gerosa RC, Boettcher S, Kovtonyuk LV, Hausmann A, Hardt WD, Hidalgo J, Nombela-Arrieta C, Manz MG (2021) CXCL12-abundant reticular cells are the major source of IL-6 upon LPS stimulation and thereby regulate hematopoiesis. Blood Adv 5:5002–5015

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Y, Li B, Ning B (2022) Evaluating IL-6 and IL-10 as rapid diagnostic tools for Gram-negative bacteria and as disease severity predictors in pediatric sepsis patients in the intensive care unit. Front Immunol 13:1043968

Article  CAS  PubMed  PubMed Central  Google Scholar 

Merz C, von Massenhausen A, Queisser A, Vogel W, Andren O, Kirfel J, Duensing S, Perner S, Nowak M (2016) IL-6 overexpression in ERG-positive prostate cancer is mediated by prostaglandin receptor EP2. Am J Pathol 186:974–984

Article  CAS  PubMed  Google Scholar 

Licastro F, Grimaldi LM, Bonafe M, Martina C, Olivieri F, Cavallone L, Giovanietti S, Masliah E, Franceschi C (2003) Interleukin-6 gene alleles affect the risk of Alzheimer’s disease and levels of the cytokine in blood and brain. Neurobiol Aging 24:921–926

Article  CAS  PubMed  Google Scholar 

Pereira DS, Garcia DM, Narciso FM, Santos ML, Dias JM, Queiroz BZ, Souza ER, Nobrega OT, Pereira LS (2011) Effects of 174 G/C polymorphism in the promoter region of the interleukin-6 gene on plasma IL-6 levels and muscle strength in elderly women. Braz J Med Biol Res 44:123–129

Article  CAS  PubMed  Google Scholar 

Walston J, Arking DE, Fallin D, Li T, Beamer B, Xue Q, Ferrucci L, Fried LP, Chakravarti A (2005) IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. Exp Gerontol 40:344–352

Article  CAS  PubMed  Google Scholar 

Zhang G, Zhou B, Wang W, Zhang M, Zhao Y, Wang Z, Yang L, Zhai J, Feng CG, Wang J, Chen X (2012) A functional single-nucleotide polymorphism in the promoter of the gene encoding interleukin 6 is associated with susceptibility to tuberculosis. J Infect Dis 205:1697–1704

Article  CAS  PubMed  PubMed Central  Google Scholar 

Riethmueller S, Somasundaram P, Ehlers JC, Hung CW, Flynn CM, Lokau J, Agthe M, Dusterhoft S, Zhu Y, Grotzinger J, Lorenzen I, Koudelka T, Yamamoto K, Pickhinke U, Wichert R, Becker-Pauly C, Radisch M, Albrecht A, Hessefort M, Stahnke D, Unverzagt C, Rose-John S, Tholey A, Garbers C (2017) Proteolytic origin of the soluble human IL-6R in vivo and a decisive role of N-glycosylation. PLoS Biol 15:e2000080

Article  PubMed  PubMed Central  Google Scholar 

Lust JA, Donovan KA, Kline MP, Greipp PR, Kyle RA, Maihle NJ (1992) Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor. Cytokine 4:96–100

Article  CAS  PubMed  Google Scholar 

Wilkinson AN, Gartlan KH, Kelly G, Samson LD, Olver SD, Avery J, Zomerdijk N, Tey SK, Lee JS, Vuckovic S, Hill GR (2018) Granulocytes are unresponsive to IL-6 due to an absence of gp130. J Immunol 200:3547–3555

Article  CAS  PubMed  Google Scholar 

Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T (1990) Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63:1149–1157

Article  CAS  PubMed  Google Scholar 

Boulanger MJ, Chow DC, Brevnova EE, Garcia KC (2003) Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science 300:2101–2104

Article  CAS  PubMed  Google Scholar 

Heink S, Yogev N, Garbers C, Herwerth M, Aly L, Gasperi C, Husterer V, Croxford AL, Moller-Hackbarth K, Bartsch HS, Sotlar K, Krebs S, Regen T, Blum H, Hemmer B, Misgeld T, Wunderlich TF, Hidalgo J, Oukka M, Rose-John S, Schmidt-Supprian M, Waisman A, Korn T (2017) Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells. Nat Immunol 18:74–85

Article  CAS  PubMed  Google Scholar 

Gadient RA, Otten U (1994) Identification of interleukin-6 (IL-6)-expressing neurons in the cerebellum and hippocampus of normal adult rats. Neurosci Lett 182:243–246

Article  CAS  PubMed  Google Scholar 

Gadient RA, Otten U (1994) Expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) mRNAs in rat brain during postnatal development. Brain Res 637:10–14

Article  CAS  PubMed  Google Scholar 

Marz P, Cheng JG, Gadient RA, Patterson PH, Stoyan T, Otten U, Rose-John S (1998) Sympathetic neurons can produce and respond to interleukin 6. Proc Natl Acad Sci U S A 95:3251–3256

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sallmann S, Juttler E, Prinz S, Petersen N, Knopf U, Weiser T, Schwaninger M (2000) Induction of interleukin-6 by depolarization of neurons. J Neurosci 20:8637–8642

Article  CAS  PubMed  PubMed Central  Google Scholar 

Van Wagoner NJ, Oh JW, Repovic P, Benveniste EN (1999) Interleukin-6 (IL-6) production by astrocytes: autocrine regulation by IL-6 and the soluble IL-6 receptor. J Neurosci 19:5236–5244

Article  PubMed  PubMed Central  Google Scholar 

Banks WA, Kastin AJ, Gutierrez EG (1994) Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci Lett 179:53–56

Article  CAS