The Pathophysiologic Role of Monocytes and Macrophages in Systemic Lupus Erythematosus: A Reappraisal

Objectives: To review current developments, regarding the pathophysiologic role of monocytes and macrophages in systemic lupus erythematosus (SLE). Methods: We searched Medline for articles written in the English language using the following terms: monocyte(s) or macrophage(s) and lupus. Although our search spanned the years 1971 to 2008, the majority of the short-listed articles belonged to the period 2000 to 2008. Published literature on phenotypic and functional properties of monocytes/macrophages (Mo/M phi) in SLE was reviewed. References from identified articles were also selected. Currently available experimental data and their relevance to the pathogenesis of SLE are critically discussed. Results: It has traditionally been held that impaired phagocytosis by monocytes and macrophages in SLE allows for the accumulation of apoptotic debris leading to a sequel of autoimmune phenomena. Recent paradigms derived from animal models of systemic autoimmunity, however, has broadened our understanding regarding the possible pathophysiologic roles of Mo/M phi in SLE. Data derived from studies in patients with SLE show multiple aberrations in activation status and secretory functions of circulating and tissue-infiltrating Mo/M phi. Such aberrations may be associated with dysregulation of T-cell function and autoantibody production in SLE. Moreover, emerging evidence suggests that phagocytic capacity and antigen-presenting properties of Mo/M phi are enhanced in some patients with SLE. Conclusions: While defective phagocytosis represents a distinctive feature of monocyte function in some patients with SLE, aberrant activation of the Mo/M phi system may be a more appropriate concept to encompass the broad spectrum of Mo/M phi disorders in SLE. Aberrant function of lupus Mo/M phi appears to play a dynamic role in the initiation and perpetuation of the systemic autoimmune response and organ damage. Delineation of the altered biology of lupus Mo/M phi could provide possible future therapeutic targets for patients with SLE. 2010 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 39:491-503