title: Is antibody therapy of tumor compromised by infusion-related reactions? A case for inhibiting the activity of cyclooxygenase-2.
abstract: Evidence suggests that amelioration of childhood immune thrombocytopenic purpura and some other autoimmune states by intravenous normal IgG is due to the following chain of events: (1) cross-linking of Fcgamma-receptors on blood effector cells; (2) release of mediators from these cells, often yielding an infusion-related reaction; (3) mediator-induced development of a cytokine field characterized by a mutually stabilizing Th2 polarization of CD4 T lymphocytes and alternative activation of macrophages; (4) selective quiescence of these macrophages towards targets coated with IgG autoantibody, due to increased expression of the macrophage Fcgamma-receptor IIB. In this paper it is postulated that in the field of antibody therapy of tumor, an undesirable delayed or absent subsidence of antibody-coated tumor is due to immunomodulation of the same type as yields amelioration of autoimmunity, and arising from a similar chain of events. If the postulate is correct the chain could usefully be broken at the level of mediator action, possibly by blocking that increased synthesis of prostaglandin E(2) which is catalyzed by the enzyme cyclooxygenase-2.
authors.affiliation: Tenovus Research Laboratory, Southampton University Hospitals, Southampton SO16 6YD, UK.
authors.forename: George T
authors.initials: GT
authors.lastname: Stevenson
mesh_terms: D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy; D002648:Child; D051546:Cyclooxygenase 2; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects*; D007167:Immunotherapy / Q000009:adverse effects*; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
chemical_list: D016756:Immunoglobulins, Intravenous; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases