MR16-1 / Roche - LARVOL DELTA

Anti-IL-6 Receptor Antibody Suppresses Visual Dysfunction in AQP4 Peptide-Immunized Mice. (PubMed, Transl Vis Sci Technol) - "To investigate whether an anti-interleukin-6 (IL-6) receptor antibody (MR16-1) can prevent retinal and optic nerve dysfunction, as well as myelitis, in a mouse model of myelitis induced by immunization with aquaporin-4 (AQP4) peptide...Retinal function was assessed by electroretinography (ERG), including b-wave, a-wave, and positive scotopic threshold response (pSTR) amplitudes...These findings support the therapeutic potential of IL-6 inhibition in preserving visual function in neuromyelitis optica spectrum disorder (NMOSD). IL-6 receptor blockade may be a viable strategy for preventing visual impairment in patients with NMOSD."

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

IL-6 blockade at the fracture site accelerates bone healing via inflammatory modulation of sensory nerve CGRP signaling. (PubMed, Int Immunopharmacol) - "These results suggest that local administration of MR16-1 may enhance CGRP expression, promote callus maturation, and accelerate fracture healing, indicating a potential role in bone repair."

Journal • Inflammation • Musculoskeletal Diseases • Oncology • Orthopedics • CD68 • CD86 • CTSK • IL10 • IL1B • IL6 • MRC1 • NFATC1 • RUNX2 • SOST • TGFB1 • TNFA

Interleukin-6 blockade modulates monocyte recruitment to protect against diastolic dysfunction associated with inflammatory arthritis. (PubMed, Arthritis Res Ther) - "Treatment of arthritic mice with an antibody that blocks IL-6 signalling is effective in preventing functional alterations of the heart, likely consequent to regulation of monocyte recruitment, and reductions in numbers of pro-inflammatory macrophages and fibroblasts. These preclinical data could prompt specific studies to determine the efficacy of anti-IL-6 therapy in patients at increased risk of cardiac alterations that lead to heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CCR2 • IL6 • LGALS3 • MRC1 • PDPN • THY1

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

Anti–IL-6R antibody treatment changes microglial phenotype in AQP4 peptide–immunized mice, leading to suppression of myelitis severity (ECTRIMS 2025) - "Introduction: Satralizumab is approved for preventing relapses of neuromyelitis optica spectrum disorder (NMOSD). These results suggest that IL-6 signal inhibition promotes a neuroprotective phenotypic change in microglia induced by IFNg signaling, potentially suppressing the severity of myelitis."

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

Fracture-Induced Immunological Cascades Trigger Rapid Systemic Bone Loss via Osteocyte-Regulated Osteoclastogenesis. (PubMed, Immunotargets Ther) - "Furthermore, fractured mice were treated with MR16-1 (monoclonal anti-mouse IL-6 receptor antibody) or Stattic...This study demonstrates that IL-6 drives osteoclast-mediated bone resorption via STAT3-dependent RANKL induction in osteocyte, thereby aggravating post-fracture systemic bone loss. And the findings highlight that modulating the IL-6/STAT3/RANKL axis and targeting osteocyte function may offer a promising therapeutic approach for preventing bone loss and minimizing the risk of fracture recurrence."

Journal • Inflammation • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • IL6 • TNFSF11

Anti-IL-6R antibody treatment changes microglial phenotype in AQP4 peptide-immunized mice, leading to suppression of myelitis severity. (PubMed, J Neuroimmunol) - "Satralizumab, an anti-interleukin-6 receptor (anti-IL-6R) antibody, has been proven in previous studies to reduce the frequency and severity of relapses in patients with NMOSD. Mice treated with MR16-1 showed a greater percentage of CD11c+ microglia in the spinal cord, along with upregulated expression of phagocytosis-related genes. Blockade of IL-6R by anti-IL-6R antibodies may suppress the severity of myelitis by increasing CD11c+ microglia and enhancing phagocytic function in AQP4 peptide-immunized mice."

Journal • Preclinical • CNS Disorders • Immunology • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • ITGAX

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

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