Progression of disease and a remedy: causative role of macrophages and microglia: remedial effect of immunomodulatory and immunosuppressive therapies "in combination".

The possibility of a pathway, common to progression, in entities in which activated macrophages or microglia are present, amenable to particular therapies, is discussed. Immunoglobulin synthesis and activation of the complement pathway may be critical elements in progression. It is possible progression in a proportion of patients may be lessened by immunomodulatory and immunosuppressive therapies in "combination", immunomodulatory therapies inhibiting the antigen presenting cell, and immunosuppressive therapies lymphocyte immunoglobulin synthesis. Such "combination therapy" may inhibit more effectively immunoglobulin synthesis and complement pathway activation, thus "downregulating" activated microglia or macrophages. In this perspective, the disease phenotype reflects the particular cell or tissue targeted by activated microglia or macrophages, a form of "auto-immunity", devoid of the usual inflammatory markers. Amplification of immunoglobulin synthesis by the complement pathway, particularly the component, C3d, leads to progression of the process. Diseases in which such "combination" therapy might lessen the rate of decline include Alzheimer's disease, Parkinson's disease, multiple sclerosis, macular degeneration, and diabetes.