Interleukin 12 subunit p40 inhibitor / Angelini Group - LARVOL DELTA

Susceptibility Analysis in Several Mouse Strains Reveals Robust T-Cell Responses After Mycoplasma pneumoniae Infection in DBA/2 Mice. (PubMed, Front Cell Infect Microbiol) - "Thus, DBA/2 may be an appropriate strain for evaluating Mp infection. Moreover, a comparison of responses revealed by various inbred mouse strains could be useful for elucidating the pathogenesis of Mycoplasma pneumonia."

Journal • Immunology • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • IL12A • PTPRC

Aberrant Methylation of miR-34b and IL-12B mRNA Promoters Contributes to the Reduced Severity of Ankylosing Spondylitis. (PubMed, Biochem Genet) - "Luciferase assays with the transfection of miR-34b precursors suggested that miR-34b strongly suppressed the expression of IL-12B in THP-1 cells. In conclusion, our study demonstrated that hypermethylated miR-34b promoter led to evident upregulation of miR-34b, thus inhibiting the expression of IL-12B and alleviated the severity of ankylosing spondylitis by reducing the levels of factors including ASDAS-CRP, BASFI and BASMI."

Journal • Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

Interleukin 12p40 Deficiency Promotes Abdominal Aortic Aneurysm by Activating CCN2/MMP2 Pathways. (PubMed, J Am Heart Assoc) - "Conclusions Our study reveals novel roles for IL12p40 deficiency in inducing fibro-proteolytic activities in the aneurysmal mouse model. Mechanistically, these effects of IL12p40 deficiency are mediated by CCN2/matrix metalloproteinase-2 crosstalk in the medial layer of aneurysmal aortae."

IO biomarker • Journal • Cardiovascular • Fibrosis • Immune Modulation • Inflammation • ALK • ALK1 • APOE • BTC • CD40LG • CTGF • ELANE • IL12A • IL13 • IL17A • IL5 • MMP2 • PCR

Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment. (PubMed, Front Pharmacol) - "The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247."

Biomarker • Clinical • Journal • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • HGF • IL12A • IL6 • PAI1 • VCAM1

Concomitant use of an immunomodulator with ustekinumab as an induction therapy for Crohn's disease: A systematic review and meta-analysis. (PubMed, J Gastroenterol Hepatol) - "The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST."

Journal • Retrospective data • Review • Crohn's disease • Gastroenterology • Immune Modulation • Immunology • Inflammation • Inflammatory Bowel Disease • IL12A

Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials. (PubMed, RMD Open) - P3 | "Improvements in BASDAI neck/back/hip pain and mBASDAI among ustekinumab-treated, TNFi-naïve, PsA patients with PA-PRS were clinically meaningful and consistent across assessment tools. Numerically greater improvements in neck/back/hip pain in HLA-B27 than HLA-B27 n n patients, noted in the context of similar overall mBASDAI improvements between the subgroups, suggest ustekinumab may improve disease activity in TNFi-naïve PsA patients likely to exhibit axial disease."

Clinical • Journal • P3 data • Ankylosing Spondylitis • Fatigue • Immunology • Pain • Psoriasis • Psoriatic Arthritis • Rheumatology

Toll-like receptor linked cytokine profiles in cerebrospinal fluid discriminate neurological infection from sterile inflammation. (PubMed, Brain Commun) - "It is especially relevant to the commonly encountered pathologies in clinical practice, such as subarachnoid haemorrhage and post-cranial neurosurgery. While requiring confirmation in a larger cohort, the current data indicate the potential utility of cerebrospinal fluid biomarker strategies to identify differential initiation of a common downstream interleukin-6 pathway to diagnose nosocomial infection in this challenging clinical cohort."

IO biomarker • Journal • CNS Disorders • Hypertension • Immunology • Infectious Disease • Inflammation • Subarachnoid Hemorrhage • Ventriculomegaly • IL17A • IL6

Immunology of IL-12: An update on functional activities and implications for disease. (PubMed, EXCLI J) - "We will begin with a summary on structure and function of the cytokine itself as well as its receptor and outline the signal transduction and the transcriptional regulation of IL-12 secretion. In the second part of the review, we will depict the involvement of IL-12 in immune-mediated diseases and relevant experimental disease models, while also providing an outlook on potential translational approaches."

Journal • Review • CNS Disorders • Immunology • Inflammation • Psychiatry

Linarin Protects the Kidney against Ischemia/Reperfusion Injury via the Inhibition of Bioactive ETS2/IL-12. (PubMed, Biol Pharm Bull) - "In addition, according to molecular docking the contact area is highly conserved and located on a PPI domain of ETS2 which indicates that LIN may alter the interaction with synergistic proteins in the regulation of IL-12 p40 expression. Our study demonstrated the anti-inflammatory effect of LIN during IRI-AKI, broadening the medicinal value of LIN and the therapeutic options for IRI-AKI."

Journal • Acute Kidney Injury • Immunology • Inflammation • Nephrology • Oncology • Renal Disease • Reperfusion Injury

All are Equal, Some are More Equal: Targeting IL 12 and 23 in IBD - A Clinical Perspective. (PubMed, Immunotargets Ther) - "Ustekinumab is an antibody that blocks p40 and thereby interleukins 12 and 23. Consequently, new questions arose about the distinct features of IL 12 and 23. This review focuses on these interleukins regarding their functions in the healthy and inflamed gut and provides an overview about the results from in vitro and in vivo studies as well as clinical trials."

Clinical • Journal • Review • Crohn's disease • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Psoriasis • Ulcerative Colitis

Evolution of neuroinflammation across the lifespan of individuals with Down syndrome. (PubMed, Brain) - "Finally, multivariate projection methods identified specific cytokine patterns among individuals with Down syndrome. Our findings indicate the presence of an early and evolving neuroinflammatory phenotype across the lifespan in Down syndrome, a knowledge that is relevant for the discovery of stage-specific targets and for the design of possible anti-inflammatory trials against Alzheimer's disease in this population."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders • Immunology • Inflammation • CCL22 • IL10 • IL15 • IL6

Toll-like receptor 4 regulates intestinal fibrosis via cytokine expression and epithelial-mesenchymal transition. (PubMed, Sci Rep) - "Colon fibrosis was induced in TLR4-deficient (TLR4) mice and its wild-type counterparts with 3% dextran sulfate sodium. Suppression of TLR4 transcription by siRNAs affected myofibroblasts activity, collagen synthesis, and EMT in the human cancer cell line. Thus, we suggest that TLR4 can be an essential mediator in intestinal chronic inflammation and fibrosis, indicating that TLR4 signaling is a potential therapeutic target for intestinal fibrosis."

IO Biomarker • Journal • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation

New insights into the IL-12 and IL-23: from a molecular basis to clinical application in immune-mediated inflammation and cancers. (PubMed, Biochem Pharmacol) - "This review focuses on IL-12/IL-23 signal transduction and biological functionality in autoimmunity and oncoimmunology. We discuss the therapeutic rationale for targeting these cytokines to treat immune-mediated diseases and issues regarding their inadvertent consequences in the balance of host defense and tumor surveillance and summarize their recent clinical applications in immune-mediated diseases."

Clinical • IO Biomarker • Journal • Review • Immunology • Inflammation • Oncology

[VIRTUAL] A Drug Reaction to Ustekinumab in a Patient With Crohn’s Disease (ACG 2020) - "Case Description/ A 42 year old man with a complicated 25 year history of ileocolonic CD, prior ileocolic resection for a colonic stricture, and partial left hemicolectomy for a colo-cutaneous fistula and abdominal abscess while on adalimumab presented with abdominal pain after 4 years without follow up...He received 4 days of premedication with acetaminophen, famotidine, prednisone, and diphenhydramine before his maintenance dose of 90 mg subcutaneously without any reaction...If we extrapolate from anti-TNF literature, non-antibody reactions may be able to be managed with short term topical or systemic therapy and without necessarily discontinuing the drug. Treatment should occur on a case-by-case basis because reported dermatologic reactions are so few in number."

Clinical • Atopic Dermatitis • Crohn's disease • Dermatology • Gastroenterology • Hematological Malignancies • Immunology • Inflammatory Bowel Disease • Lymphoma • Oncology • Pain • Psoriasis • Urticaria • IL12A

miR-520a-3p regulates the signaling pathway of cytokine secretion in cervical cancer (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "miR-520a-3p inhibits cytokine secretion in HELA cells of cervical cancer by targeting RELA, a key molecule in the NF-κB signaling pathway."

Journal • Cervical Cancer • Solid Tumor • CCL2 • CCL5 • CSF2 • IFNG • IL10 • IL12A • IL13 • IL17A • IL2 • IL4 • IL5 • IL6 • IL9 • TNFA

March of Mycobacterium: miRNAs intercept host cell CD40 signalling. (PubMed, Clin Transl Immunology) - "The CD40-CD40L-induced counteractive immune responses against Mycobacterium thus present a conundrum that we explain here with a reconciliatory hypothesis. Experimental validation of the hypothesis will provide a rationale for designing anti-tubercular immunotherapy."

IO Biomarker • Journal • Review • Immune Modulation • Immunology • Infectious Disease • Inflammation • Tuberculosis • CD40LG • IL10

Nicotinamide inhibits melanoma in vitro and in vivo. (PubMed, J Exp Clin Cancer Res) - "NAM shows a relevant anti-melanoma activity in vitro and in vivo and is a suitable candidate for further clinical investigations."

Journal • Preclinical • Melanoma • Oncology • Solid Tumor • CCL11 • CCL5 • IFNG • IL10 • IL12A • IL5

Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti-Interleukin 12/23p40 Antibody Ustekinumab. (PubMed, JAMA Dermatol) - "In line with the current mechanistic models for atherosclerotic disease, the period after the initiation of anti-IL-12/23p40 may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17. Although the study interpretation is limited by its observational design, these results suggest that caution may be needed in the prescription of ustekinumab to patients at high cardiovascular risk."

Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Crohn's disease • Dermatology • Dyslipidemia • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

[VIRTUAL] FUNCTIONAL IMMUNE RECONSTITUTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A COMPARISON OF PRE- AND POST-TRANSPLANTATION CYTOKINE RESPONSES IN STIMULATED WHOLE-BLOOD (EBMT 2020) - "Our study revealed a significant functional immune dysfunction in patients pre-HSCT. Post-HSCT, the functional immune reconstitution was heterogenous: the cytokine responses to LPS, R848 and HCKA (but not Poly-I:C) were generally improved, despite that patients received immunosuppressive prophylaxis post-HSCT. R848 and HKCA elicited a greater cytokine response in patients post-HSCT than in healthy individuals, whereas the post-HSCT responses to LPS and Poly-I:C remained less than normal for most cytokines."

Graft versus Host Disease • Immunology • Transplantation • CXCL8 • IFNG • IL10 • IL17A • IL1B • IL6 • TNFA

[VIRTUAL] FUNCTIONAL IMMUNE RECONSTITUTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A COMPARISON OF PRE- AND POST-TRANSPLANTATION CYTOKINE RESPONSES IN STIMULATED WHOLE-BLOOD (EBMT 2020) - "Our study revealed a significant functional immune dysfunction in patients pre-HSCT. Post-HSCT, the functional immune reconstitution was heterogenous: the cytokine responses to LPS, R848 and HCKA (but not Poly-I:C) were generally improved, despite that patients received immunosuppressive prophylaxis post-HSCT. R848 and HKCA elicited a greater cytokine response in patients post-HSCT than in healthy individuals, whereas the post-HSCT responses to LPS and Poly-I:C remained less than normal for most cytokines."

Graft versus Host Disease • Immunology • Transplantation • CXCL8 • IFNG • IL10 • IL17A • IL1B • IL6 • TNFA

[VIRTUAL] FUNCTIONAL IMMUNE RECONSTITUTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A COMPARISON OF PRE- AND POST-TRANSPLANTATION CYTOKINE RESPONSES IN STIMULATED WHOLE-BLOOD (EBMT 2020) - "Our study revealed a significant functional immune dysfunction in patients pre-HSCT. Post-HSCT, the functional immune reconstitution was heterogenous: the cytokine responses to LPS, R848 and HCKA (but not Poly-I:C) were generally improved, despite that patients received immunosuppressive prophylaxis post-HSCT. R848 and HKCA elicited a greater cytokine response in patients post-HSCT than in healthy individuals, whereas the post-HSCT responses to LPS and Poly-I:C remained less than normal for most cytokines."

Graft versus Host Disease • Immunology • Transplantation • CXCL8 • IFNG • IL10 • IL17A • IL1B • IL6 • TNFA

[VIRTUAL] FUNCTIONAL IMMUNE RECONSTITUTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A COMPARISON OF PRE- AND POST-TRANSPLANTATION CYTOKINE RESPONSES IN STIMULATED WHOLE-BLOOD (EBMT 2020) - "Our study revealed a significant functional immune dysfunction in patients pre-HSCT. Post-HSCT, the functional immune reconstitution was heterogenous: the cytokine responses to LPS, R848 and HCKA (but not Poly-I:C) were generally improved, despite that patients received immunosuppressive prophylaxis post-HSCT. R848 and HKCA elicited a greater cytokine response in patients post-HSCT than in healthy individuals, whereas the post-HSCT responses to LPS and Poly-I:C remained less than normal for most cytokines."

Graft versus Host Disease • Immunology • Transplantation • CXCL8 • IFNG • IL10 • IL17A • IL1B • IL6 • TNFA

Dose-dependent effects of two inulin types differing in chain length on the small intestinal morphology, contractility and proinflammatory cytokine gene expression in piglets. (PubMed, Arch Anim Nutr) - "In conclusion, IN10 is more active in the small intestine than IN23. At the 2% dietary level, it increases absorptive area in the jejunum, but may slightly impair smooth muscle contractions."

Journal

Discovery of Cell-Surface Vimentin (CSV) as a Sarcoma Target and Development of CSV-Targeted IL12 Immune Therapy. (PubMed, Adv Exp Med Biol) - "This CSV-targeted delivery of IL12 also reduced toxicity of IL12. In summary, this chapter details a novel approach for safe IL12 immune therapy via targeting CSV."

Journal • Gene Therapies • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Amino acid residues involved in the heparin-binding activity of murine IL-12 in the context of an antibody-cytokine fusion protein. (PubMed, Cytokine) - "However, the IL-12 bioactivity is decreased compared to its non-mutated counterpart, which is consistent with an ancillary role of the heparin-binding site of IL-12 in modulating its activity. Thus, we have defined a cluster of amino acid residues with a crucial role in the heparin-binding activity of murine IL-12 in the context of an antibody-cytokine fusion protein."

Journal • Preclinical • Oncology