GOLIMUMAB IS A HUMAN IGG1K MONOCLONAL ANTIBODY SPECIFIC FOR HUMAN TUMOR NECROSIS FACTOR ALPHA (TNFA). GOLIMUMAB IS A HUMAN MONOCLONAL ANTIBODY THAT BINDS TO BOTH THE SOLUBLE AND TRANSMEMBRANE BIOACTIVE FORMS OF HUMAN TNF?. THIS INTERACTION PREVENTS THE BINDING OF TNF? TO ITS RECEPTORS, THEREBY INHIBITING THE BIOLOGICAL ACTIVITY OF TNF? (A CYTOKINE PROTEIN). THERE WAS NO EVIDENCE OF THE GOLIMUMAB ANTIBODY BINDING TO OTHER TNF SUPERFAMILY LIGANDS; IN PARTICULAR, THE GOLIMUMAB ANTIBODY DID NOT BIND OR NEUTRALIZE HUMAN LYMPHOTOXIN. GOLIMUMAB DID NOT LYSE HUMAN MONOCYTES EXPRESSING TRANSMEMBRANE TNF IN THE PRESENCE OF COMPLEMENT OR EFFECTOR CELLS.
ELEVATED TNF? LEVELS IN THE BLOOD, SYNOVIUM, AND JOINTS HAVE BEEN IMPLICATED IN THE PATHOPHYSIOLOGY OF RHEUMATOID ARTHRITIS. TNF? IS AN IMPORTANT MEDIATOR OF THE ARTICULAR INFLAMMATION THAT IS CHARACTERISTIC OF RA. GOLIMUMAB MODULATED THE IN VITRO BIOLOGICAL EFFECTS MEDIATED BY TNF IN SEVERAL BIOASSAYS, INCLUDING THE EXPRESSION OF ADHESION PROTEINS RESPONSIBLE FOR LEUKOCYTE INFILTRATION (E-SELECTIN, ICAM-1 AND VCAM-1) AND THE SECRETION OF PROINFLAMMATORY CYTOKINES (IL-6, IL-8, G-CSF AND GM-CSF). THE CLINICAL RELEVANCE OF THESE FINDINGS IS UNKNOWN.