The aim of this study was to assess the effect of adalimumab on the expression level of mRNA and protein TNF-α, IFN-γ, IL-17, IL12A, IL12B, and IL23A in the culture of normal human fibroblasts, in which the LPS inflammation process was induced. The NHDF culture was exposed to the effect of LPS in the concentrations of 1, 2, and 10 μg/mL for 2, 8, and 24 hour periods, and then adalimumab was added at the concentration of 8 μg/mL, it was then incubated for 2, 8, and 24 hour. Cells unexposed to LPS and adalimumab constituted the control. The microarray expression techniques, RTqPCR, and ELISA assay were used. Irrespectively of the concentration of LPS used and the incubation time of it with cells overexpression of the analyzed genes is present, with increasing factor concentration used to induce inflammation and incubation time with it, expression of the assessed genes was greater. In turn, adding the anti-TNF drug to the culture caused the silencing of the expression of the mRNAs and proteins. It was confirmed that LPS and adalimumab above all affect the expression of genes and proteins dependent on the interaction of IL-12 with receptors, which are TNF-α and IFN-γ, and to a lesser extent also modulate IL-17.
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http://dx.doi.org/10.1111/dth.13400 | DOI Listing |
Background: Axial Spondyloarthritis (axSpA) is a chronic inflammatory rheumatic condition affecting the axial skeleton, leading to pain, stiffness, and fatigue. While biologic therapies have improved clinical management, many patients experience partial or no responses, resulting in delays in disease control. Additionally, the risk of adverse events and increased costs remains a concern.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Introduction: Immunogenicity continues to be a challenge for development and clinical utility of monoclonal antibodies, and there are gaps in our current ability to prevent anti-drug antibody development in a safe and antigen-specific manner.
Methods: To mitigate immunogenicity of monoclonal antibodies administered subcutaneously, O-phospho-L-serine (OPLS)-the head group of the tolerance-inducing phospholipid, phosphatidylserine-was investigated as an immunoregulatory adjuvant.
Results: Formulations of adalimumab, trastuzumab or rituximab with OPLS showed reduction in relative immunogenicity in mice compared to vehicle formulations, indicated by reduced anti-drug antibody development and significant reductions in CD138+ plasma cell differentiation in bone marrow.
Int J Pharm
November 2024
Molecular Imaging and Pharmacokinetic Modelling Group, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Nuclear Medicine and Molecular Imaging Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Monoclonal antibodies targeting tumor necrosis factor-alpha (antiTNF-α) are used for patients with immuno-mediated illness as inflammatory bowel disease (IBD). However, 20-40 % of IBD patients do not respond to these therapies, and increasing knowledge of biodistribution could optimize their use and consequently their effectiveness. The aim of this study is to compare the biodistribution of adalimumab after intravenous (IV) and subcutaneous (SC) administration using Positron Emission Tomography (PET) imaging in IBD animal models.
View Article and Find Full Text PDFCommun Biol
November 2024
University Hospital Jena, Department of Dermatology, Friedrich Schiller University Jena, Jena, Germany.
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