Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Can intermediate monocytes predict response to infliximab therapy in sarcoidosis?

Abstract

Sarcoidosis is a systemic granulomatous disease of unknown origin that can cause a variety of symptoms, but most often affects the lungs [1]. Because sarcoidosis is self-limiting in the majority of patients, not all patients require therapy [2]. In case of severe sarcoidosis, first-line therapy consists of prednisone, with methotrexate or azathioprine being the most commonly used second-line options [3]. Infliximab, a monoclonal anti-tumour necrosis factor (TNF) drug, is an effective third-line therapeutic for severe sarcoidosis [4, 5]. The exact nature and order of immunological events leading to the formation of sarcoid granulomas remains unknown. Granulomas consist of highly differentiated mononuclear phagocytes (mainly activated macrophages) and lymphocytes [1]. Macrophages of sarcoidosis patients are known to produce excessive amounts of TNF compared with healthy controls [6, 7]. The importance of TNF is underlined by the success of infliximab therapy. As monocytes are the precursors of tissue macrophages, monocytes might be a key player in this process. A promising new therapeutic strategy for sarcoidosis is the combined monocyte and granulocyte apheresis [8]. Although only seven patients were included in a pilot study, the positive effects underline the importance of monocytes in the sarcoidosis disease process. CD16-expressing monocytes are expanded in various immune-mediated diseases, such as rheumatoid arthritis, diabetes, atherosclerosis, bacterial infections and HIV [9]. High percentages of CD16-expressing monocytes were also found in sarcoidosis patients when compared with controls [10, 11]. CD16-expressing monocytes, and intermediate monocytes in particular, fulfil a pro-inflammatory role by producing TNF as well as other cytokines [12]. We have previously shown that sarcoidosis patients have a significantly higher percentage of the pro-inflammatory intermediate monocytes than healthy controls [13], an observation that has been confirmed recently by HOFER et al. [14].