THERAPEUTIC APPROACHES TO IMMUNE COMPLEX DISEASE
The most common types of therapy in immune complex disease are based on four main approaches:
1. Eradication of the source of persistent antigen production (e.g., infections, tu-mors).
2. Turning off the inflammatory reaction (using corticosteroids and nonsteroidal agents).
3. Suppression of antibody production using immunosuppressive drugs such as cy-clophosphamide, azathioprine, or cyclosporine. This is the mainstay of IC dis-ease treatment, particularly when autoimmune reactions are on its basis.
4. Removal of soluble IC from the circulation by plasmapheresis, a procedure that consists of the removal of blood (up to 5 L each time), separation and reinfusion of red cells, and replacement of the patient’s plasma by normal plasma or plasma-replacing solutions. Plasmapheresis appears most beneficial when asso-ciated with the administration of immunosuppressive drugs; by itself, it can even induce severe clinical deterioration, perhaps related to changes in the im-munoregulatory circuits. The main drawbacks of plasmapheresis are its high cost (derived from the sophisticated equipment used and from the cost of plasma and plasma-replacing products) and the fact that it can only be adequately performed in a well-equipped medical center.
In the last few years there has been considerable interest in applying emerging basic concepts on the pathogenesis of inflammation on the treatment of a variety of conditions in which IC formation or deposition may play an important role. Three major approaches have been tried:
1. Blocking critical cytokines, such as TNF. This has been done either with mono-clonal antibodies reacting with pro-inflammatory cytokines, with cytokine re-ceptor antagonists, or with recombinant cytokine receptors. A soluble TNF-re-ceptor-Fc fusion protein, which blocks the effects of TNF, has been approved by the FDA for use in rheumatoid arthritis.
2. Interruption of the interaction between leukocyte integrins and endothelial cell adhesion molecules. Humanized anti–CAM-1 (and other cell-cell interaction-fa-cilitating molecules) as well as soluble forms of these molecules have been suc-cessfully tested in animal models.
3. Inhibition of the complement activation cascade using soluble forms of regula-tory proteins (C1 inhibitor, MCP, DAF, CR1) and antifactor antibodies (anti-C5 antibody) with the goal of inhibiting the production of C3a and C5a .
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