The role and use of recombinant receptors in the investigation and control of antibody-induced inflammation

The interaction of immune complexes with cell surface Fc receptors is a potent stimulus for the activation of inflammatory cells. In autoimmune diseases this activation process can generate widespread tissue destruction, such as vasculitis associated with rheumatoid arthritis or glomerulonephritis induced by auto-antibody deposition in systemic lupus erythematosus. Whilst the cause of autoimmunity is unknown, it is clear that immune complexes play a key role in the development of the disease pathology, through the activation of cells by complement or Fc receptors. Thus, the development of recombinant glycoproteins targeted at the neutralization of the cytotoxic mediators of immune complex-induced inflammation has been the focus of many recent investigations. Glycoproteins targeted to different mediators of the inflammation cascade limit the secretion of pro-inflammatory cytokines, act as cytokine antagonists or prevent receptor-ligand interactions. These have been developed as potential therapeutic agents in the treatment of immune complex diseases. Here we review examples of these proteins which are used to intervene in models of immune complex- or antibody-mediated diseases. Such recombinant glycoproteins could intervene at different points in the inflammation cascade but FcR blockade would also act to prevent re-presentation of antigen after complexing with Ig, i.e. could act at multiple points of immune complex formation, immune complex precipitation or re-presentation of antigen which may be responsible for perpetuation of the disease once initiated (Figure 20.1). The role of recombinant soluble Fc receptors in the regulation of immune complex-mediated models of autoimmunity is also discussed.