Kumar RG, Diamond ML, Boles JA, Berger RP, Tisherman SA, Kochanek PM, et al. Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome. Brain Behav Immun. 2015;45:253–62.

Article  CAS  PubMed  Google Scholar 

Kumar RG, Boles JA, Wagner AK. Chronic inflammation after severe traumatic brain Injury: characterization and associations with Outcome at 6 and 12 months Postinjury. J Head Trauma Rehabil. 2015;30(6):369–81.

Article  PubMed  Google Scholar 

Schreiber S, Aden K, Bernardes JP, Conrad C, Tran F, Höper H, et al. Therapeutic Interleukin-6 trans-signaling inhibition by Olamkicept (sgp130Fc) in patients with active inflammatory bowel disease. Gastroenterology. 2021;160(7):2354–e236611.

Article  CAS  PubMed  Google Scholar 

Silver JS, Hunter CA. gp130 at the nexus of inflammation, autoimmunity, and cancer. J Leukoc Biol. 2010;88(6):1145–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bao P, Liu G, Wei Y. Association between IL-6 and related risk factors of metabolic syndrome and cardiovascular disease in young rats. Int J Clin Exp Med. 2015;8(8):13491–9.

CAS  PubMed  PubMed Central  Google Scholar 

Choy E, Rose-John S. Interleukin-6 as a Multifunctional Regulator: inflammation, Immune Response, and fibrosis. J Scleroderma Relat Disord. 2017;2(2suppl):S1–5.

Google Scholar 

Burton MD, Rytych JL, Freund GG, Johnson RW. Central inhibition of interleukin-6 trans-signaling during peripheral infection reduced neuroinflammation and sickness in aged mice. Brain Behav Immun. 2013;30:66–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Garbers C, Rose-John S. Dissecting Interleukin-6 classic- and trans-signaling in inflammation and Cancer. Methods Mol Biol Clifton NJ. 2018;1725:127–40.

Article  CAS  Google Scholar 

Garner KM, Amin R, Johnson RW, Scarlett EJ, Burton MD. Microglia priming by interleukin-6 signaling is enhanced in aged mice. J Neuroimmunol. 2018;324:90–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jostock T, Müllberg J, Ozbek S, Atreya R, Blinn G, Voltz N, et al. Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem. 2001;268(1):160–7.

Article  CAS  PubMed  Google Scholar 

Berg AF, Ettich J, Weitz HT, Krusche M, Floss DM, Scheller J, et al. Exclusive inhibition of IL-6 trans-signaling by soluble gp130FlyRFc. Cytokine X. 2021;3(4):100058.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Reeh H, Rudolph N, Billing U, Christen H, Streif S, Bullinger E, et al. Response to IL-6 trans- and IL-6 classic signalling is determined by the ratio of the IL-6 receptor α to gp130 expression: fusing experimental insights and dynamic modelling. Cell Commun Signal CCS. 2019;17(1):46.

Article  PubMed  Google Scholar 

Song M, Wang Y, Annex BH, Popel AS. Experiment-based Computational Model predicts that IL-6 trans-signaling plays a Dominant Role in IL-6 mediated signaling in endothelial cells. BioRxiv Prepr Serv Biol. 2023;2023.02.03.526721.

Montgomery A, Tam F, Gursche C, Cheneval C, Besler K, Enns W, et al. Overlapping and distinct biological effects of IL-6 classic and trans-signaling in vascular endothelial cells. Am J Physiol-Cell Physiol. 2021;320(4):C554–65.

Article  CAS  PubMed  Google Scholar 

Burton MD, Johnson RW. Interleukin-6 trans-signaling in the senescent mouse brain is involved in infection-related deficits in contextual fear conditioning. Brain Behav Immun. 2012;26(5):732–8.

Article  CAS  PubMed  Google Scholar 

Campbell IL, Erta M, Lim SL, Frausto R, May U, Rose-John S, et al. Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain. J Neurosci off J Soc Neurosci. 2014;34(7):2503–13.

Article  CAS  Google Scholar 

Koper OM, Kamińska J, Sawicki K, Kemona H. CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroinflammation and neurodegeneration. Adv Clin Exp Med off Organ Wroclaw Med Univ. 2018;27(6):849–56.

Article  Google Scholar 

Lyra e Silva NM, Gonçalves RA, Pascoal TA, Lima-Filho RAS, Resende E, de PF, Vieira ELM, et al. Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease. Transl Psychiatry. 2021;11(1):251.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Scheller J, Rose-John S. Interleukin-6 and its receptor: from bench to bedside. Med Microbiol Immunol (Berl). 2006;195(4):173–83.

Article  CAS  PubMed  Google Scholar 

Bykerk VP, Ostör AJK, Alvaro-Gracia J, Pavelka K, Ivorra JAR, Graninger W, et al. Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Ann Rheum Dis. 2012;71(12):1950–4.

Article  CAS  PubMed  Google Scholar 

Petrelli F, Cherri S, Ghidini M, Perego G, Ghidini A, Zaniboni A. Tocilizumab as treatment for COVID-19: a systematic review and meta-analysis. World J Methodol. 2021;11(3):95–109.

Article  PubMed  PubMed Central  Google Scholar 

Boettger MK, Leuchtweis J, Kümmel D, Gajda M, Bräuer R, Schaible HG. Differential effects of locally and systemically administered soluble glycoprotein 130 on pain and inflammation in experimental arthritis. Arthritis Res Ther. 2010;12(4):R140.

Article  PubMed  PubMed Central  Google Scholar 

Zhang S, Chen B, Wang B, Chen H, Li Y, Cao Q, et al. Effect of induction therapy with Olamkicept vs Placebo on clinical response in patients with active Ulcerative Colitis: a Randomized Clinical Trial. JAMA. 2023;329(9):725–34.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sommer J, Garbers C, Wolf J, Trad A, Moll JM, Sack M, et al. Alternative intronic polyadenylation generates the interleukin-6 trans-signaling inhibitor sgp130-E10. J Biol Chem. 2014;289(32):22140–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lokau J, Garbers Y, Grötzinger J, Garbers C. A single aromatic residue in sgp130Fc/olamkicept allows the discrimination between interleukin-6 and interleukin-11 trans-signaling. iScience. 2021;24(11):103309.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hong J, Wang H, Shen G, Lin D, Lin Y, Ye N, et al. Recombinant soluble gp130 protein reduces DEN-induced primary hepatocellular carcinoma in mice. Sci Rep. 2016;6:24397.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schuett H, Oestreich R, Waetzig GH, Annema W, Luchtefeld M, Hillmer A, et al. Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2012;32(2):281–90.

Article  CAS  PubMed  Google Scholar 

Jackson TC, Dixon CE, Janesko-Feldman K, Vagni V, Kotermanski SE, Jackson EK, et al. Acute Physiology and neurologic outcomes after Brain Injury in SCOP/PHLPP1 KO mice. Sci Rep. 2018;8:7158.

Article  PubMed  PubMed Central  Google Scholar 

Kochanek PM, Marion DW, Zhang W, Schiding JK, White M, Palmer AM, et al. Severe controlled cortical impact in rats: assessment of cerebral edema, blood flow, and contusion volume. J Neurotrauma. 1995;12(6):1015–25.

Article  CAS  PubMed  Google Scholar 

Lagraoui M, Latoche JR, Cartwright NG, Sukumar G, Dalgard CL, Schaefer BC. Controlled cortical impact and craniotomy induce strikingly similar profiles of inflammatory gene expression, but with distinct kinetics. Front Neurol. 2012;3:155.

Article  PubMed  PubMed Central  Google Scholar 

Byrnes KR, Loane DJ, Stoica BA, Zhang J