MR16-1 / Roche - LARVOL DELTA

Anti-IL-6 receptor antibody attenuates myelitis severity of AQP4 peptide immunized mice (ECTRIMS 2024) - "Satralizumab, a novel humanized anti-IL-6 receptor (IL-6R) monoclonal recycling antibody, is used as a therapeutic for suppressing the relapse...Anti-IL-6R antibody (MR16-1) or vehicle was intraperitoneally administered on day 9... These results may suggest that IL-6 signaling promotes microglial proliferation in the spinal cord, possibly promotes severity of the spinal cord damage. Further analysis, RNA sequencing of the spinal cord, is now carrying out in order to dig the mechanism in detail."

Preclinical • CNS Disorders • Immunology • Infectious Disease • Inflammation • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • Respiratory Diseases

Anti-IL-6 Receptor Antibody Prevents Muscle Weakness in Experimental Autoimmune Myasthenia Gravis Mouse Model (AAN 2024) - "Anti-IL-6R antibody prevented development of muscle weakness and reduced anti-AChR antibody production and deposition in AChR-immunized EAMG mice."

Preclinical • CNS Disorders • Immunology • Myasthenia Gravis

Intracerebral Hemorrhage Leads to Anemia By Disrupting Erythropoiesis and Erythromyeloblastic Islands (ASH 2023) - "Treatment with MR16-1, an IL-6 antagonist, alleviated ICH-induced anemia and improved BM erythropoiesis in ICH mice, as evidenced by increased peripheral red blood cells and hemoglobin levels, elevated numbers of erythroid progenitors and terminal erythroblast...Administration of recombinant IL-6 to wild-type mice resulted in decreased levels of red blood cells and hemoglobin along with suppression of erythropoiesis in the BM. Collectively, these results suggest that ICH modulates erythropoiesis and erythromyeloblastic islands function to ultimately lead to anemia and reveal a possible therapeutic opportunity to reverse ICH-induced anemia and improve ICH prognosis by targeting IL-6."

Anemia • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • IL6

Clarification of blood-retinal barrier on AQP4-peptide immunized mice (MSMilan 2023) - "Our results suggest that AQP4 peptide immunization disrupts not only BBB but also BRB mediated by some factors such as IL-6."

Preclinical • CNS Disorders • Immunology • Infectious Disease • Inflammation • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • Respiratory Diseases • CLDN5 • IL6 • TJP1

Interleukin-6 receptor blockade improves bone healing following ischemic osteonecrosis in adolescent mice. (PubMed, Osteoarthr Cartil Open) - "Adolescent mice (12-week-old) surgically induced with JIO were treated with either saline or MR16-1, an IL-6 receptor blocker...IL-6 blockade in adolescent mice with JIO enhanced bone formation and revascularization. The findings suggest IL-6 receptor blocker as a potential medical therapy for adolescent JIO."

Journal • Preclinical • Osteoporosis • IL6R

Intradermal AQP4 peptide immunization induces clinical features of neuromyelitis optica spectrum disorder in mice. (PubMed, J Neuroimmunol) - "Administration of anti-IL-6 receptor antibody (MR16-1) inhibited the induction of clinical signs and prevented the loss of GFAP/AQP4 and deposition of complement factors in AQP4 peptide-immunized mice. This novel experimental model may contribute to further understanding the pathogenesis of NMOSD, elucidating the mechanism of action of therapeutic agents, and developing new therapeutic approaches."

Journal • Preclinical • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • GFAP

Overcoming cancer-associated fibroblast-induced immunosuppression by anti-interleukin-6 receptor antibody. (PubMed, Cancer Immunol Immunother) - "The anti-IL-6 receptor antibody could be systemically employed to overcome tumor immunosuppression and improve patient survival with various cancers. Furthermore, the tumor immunosuppression was suggested to be induced by IL-6 via HIF1α activation."

Journal • Oncology • CAFs • HIF1A • IL6R

IL-6 receptor antagonism prevents neurological disease in mice with AQP4 peptide immunization (ECTRIMS 2022) - "IL-6 receptor antagonism exerted beneficial effects in AQP4 peptide-immunized mice through prevention of infiltrating pathogenic factors into the spinal cord."

Preclinical • CNS Disorders • Immunology • Infectious Disease • Neuromyelitis Optica Spectrum Disorder • Pain • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Tuberculosis • GFAP • IL6 • SDC1

Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice. (PubMed, Am J Physiol Renal Physiol) - "We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt)...Increases in cardiac metabolites including histidine and γ-butyrobetaine were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, anti-fibrotic, and partial anti-oxidative effects in the heart of Nx-salt mice."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • Nephrology • Oncology • Renal Disease • IL1B • IL6 • TNFA

Anti-interleukin-6 receptor antibody improves allodynia and cognitive impairment in mice with neuropathic pain following partial sciatic nerve ligation. (PubMed, Int Immunopharmacol) - "The present study examined the effect of MR16-1, an anti-IL-6 receptor antibody and inhibits IL-6 activity, on allodynia and cognitive impairment in mice with neuropathic pain following partial sciatic nerve ligation (PSNL)...The findings suggest that cognitive impairment associated with neuropathic pain is mediated through changes in hippocampus induced by IL-6. These data also suggest that IL-6 mediated peripheral inflammation underlies allodynia, and IL-6 mediated inflammation in the central nervous system underlies cognitive impairment associated with neuropathic pain, and further suggest the therapeutic potential of blocking IL-6 functioning by blocking its receptor."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Immunology • Inflammation • Neuralgia • Pain • IL6R

Treatment of high fat diet-induced obese pregnant mice with IL-6 receptor antibody does not ameliorate placental function and fetal growth restriction. (PubMed, Am J Reprod Immunol) - "Treatment with MR16-1 blocks IL-6 signaling in the placenta, but has only limited effects on preventing HFD-associated placental dysfunction and offspring outcomes in mice, suggesting further mechanisms in the deterioration of placental vascularization and fetal nutrient supply as a consequence of maternal obesity."

Journal • Preclinical • Genetic Disorders • Obesity • IL6

Interleukin-6: evolving role in the management of neuropathic pain in neuroimmunological disorders. (PubMed, Inflamm Regen) - "Thus, anti-IL-6 therapies might have a potential to reduce neuropathic pain, but further investigations are warranted to clarify the effect of inhibition of IL-6 signaling on neuropathic pain associated with MS and NMOSD."

Journal • Review • CNS Disorders • Immunology • Multiple Sclerosis • Neuralgia • Neuromyelitis Optica Spectrum Disorder • Pain • Rare Diseases • IL6

New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "These results suggest that (1) our triple-cultured in vitro and in ex vivo BBB models are ideal for evaluating barrier function, leukocyte transmigration, and intracerebral transferability; (2) NMO-IgG increased the intracerebral transferability of NMO-IgG via decreasing barrier function and induced secretion of IL-6 from astrocytes causing more dysfunction of the barrier and disrupting controlled cellular infiltration; and (3) satralizumab, which can pass through the BBB in the presence of NMO-IgG, suppresses the BBB dysfunction and the infiltration of inflammatory cells, leading to prevention of onset of NMOSD."

Journal • CNS Disorders • Immunology • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Inhibition of Interleukin-6 Signaling Attenuates Aortitis, Left Ventricular Hypertrophy and Arthritis in Interleukin-1 Receptor Antagonist Deficient Mice. (PubMed, Clin Sci (Lond)) - "The aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice...The aim of this study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice.  Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks.  These mice were stratified into 4 groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0..."

Journal • Preclinical • Immunology • Rheumatology • IL6

Pristane/Hypoxia (PriHx) Mouse as a Novel Model of Pulmonary Hypertension Reflecting Inflammation and Fibrosis. (PubMed, Circ J) - "A PriHx model, a novel mouse model of PH reflecting the pathological features of CTD-PAH, was developed through a combination of pristane administration and exposure to chronic hypoxia."

Journal • Preclinical • Fibrosis • Hypertension • Immunology • Pulmonary Arterial Hypertension

Clinical and economic implications of upper gastrointestinal adverse events in Asian rheumatological patients on long-term non-steroidal anti-inflammatory drugs. (PubMed, Int J Rheum Dis) - "The economic burden of GI adverse events due to long-term NSAIDs use in Malaysian patients with chronic rheumatic diseases is modest."

Adverse events • Clinical • Journal • Biosimilar • CNS Disorders • Immunology • Inflammation • Inflammatory Arthritis • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology

Involvement of IL-6 and GSK3β in impaired sensorimotor gating induced by high-fat diet. (PubMed, Neurosci Res) - "Interestingly, MR16-1 administration during the HFD period ameliorated PPI deficits...These results suggest that increased IL-6 levels during HFD may induce sensorimotor gating deficits, likely through the alteration of striatal GSK3β phosphorylation. MR16-1 might have a beneficial effect on such HFD-induced sensorimotor gating deficits."

Journal

The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed destructive arthritis and enthesitis. (PubMed, BMC Musculoskelet Disord) - "Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification."

Journal • Preclinical

Role and mechanism of the Th17/Treg cell balance in the development and progression of insulin resistance. (PubMed, Mol Cell Biochem) - "After establishing an insulin-resistant rat model, the rats were injected with anti-mouse IL-6R receptor antibody (MR16-1) to block IL-6...Insulin resistance can cause inflammation and an imbalance in Th17 cells/Treg cells. IL-6 can restore this imbalance and play an important role in the development and progression of insulin resistance."

Journal

EP4 Signaling in Smooth Muscle Cells Causes Abdominal Aortic Aneurysm by Attraction of Immune Infiltrates (AHA 2019) - "FACS analysis showed that infiltration of Ly6C hi inflammatory monocytes in to the aorta was greater in EP4-Tg compared to non-transgenic treated with AngII for 4days (n=4, p<0.01), which was attenuated systemic administration of MR16-1, an anti-IL-6 receptor antibody...Immunohistochemistry showed that phosphorylated TAK1 and IL-6 were upregulated in human AAA VSMCs (n=7). These data suggested that EP4 signaling in VSMCs increased IL-6 secretion via TAK1 pathway and subsequent Ly6C hi monocyte infiltration into the aorta, and promoted lysosomal LOX degradation."

Excessive Salt Intake Increases Peritoneal Local Production of Interleukin-6 and Baseline Peritoneal Solute Transport Rate in Subtotal Nephrectomized Mice (KIDNEY WEEK 2019) - "Locally overexpressed IL-6 was functionally blocked by rat anti mouse IL-6 receptor antibody (MR16-1) in another study to examine the role of IL-6 in this process...Upregulation of IL-6 under hypertonicity induced by NaCl was also observed in mouse peritoneal-derived macrophages and bone marrow-derived M1 macrophages. Conclusion These findings suggest that high salt intake under uremic condition could increase peritoneal local IL-6 production leading to higher peritoneal solute transport rate."

Preclinical

Anti-IL-6 receptor antibody improves pain symptoms in mice with experimental autoimmune encephalomyelitis. (PubMed, J Neuroimmunol) - "These findings suggest that MR16-1 can decrease mechanical allodynia in EAE mice through inhibition of microglial activation and proliferation in the spinal cord."

Journal

Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure. (PubMed, JACC Basic Transl Sci) - "Accordingly, treatment of S16D-Hsp20 mice with a rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) attenuated interstitial fibrosis and preserved cardiac function. These findings suggest that phosphorylated Hsp20 may be a potential therapeutic target in heart failure."

Journal

Anti-IL-6 Receptor Antibody Inhibits Spontaneous Pain at the Pre-onset of Experimental Autoimmune Encephalomyelitis in Mice. (PubMed, Front Neurol) - "Promotion of spinal 5-HT turnover and reduction of PAG activity were observed in pre-onset EAE mice. These results suggest that MR16-1 prevented spontaneous pain developed before EAE onset."

Journal • Preclinical

Interleukin-6 regulates psoriasis-like dermatitis induced by blockade of programmed cell death 1 signaling (SID 2019) - "To identify the roles of IL-6 in its pathogenesis, a murine model of imiquimod (IMQ)-induced psoriasiform dermatitis was used, by which we analyzed the difference between PD-1 deficient (PD-1-/-) mice and wild-type (WT) mice. In addition, MR16-1 treated PD-1-/- mice showed significantly suppressed mRNA levels in the ear skins and serum levels of psoriasis-related cytokines including IL-6, IFN-γ, IL-17A and IL-23 than those of control PD-1-/- mice. Hence, IL-6 blockade is a potential therapy to control anti-PD-1 antibody-induced psoriasisiform dermatitis."