High mobility group box 1 (HMGB-1) protein has been widely studied as a DNA-binding nuclear protein that regulates gene transcription, maintains nucleosome structure and modulates the activity of steroid hormone receptors [1]. Besides these classical functions as transcription factor, HMGB-1 may also be released by the cells into the extracellular milieu. This release process may be clearly distinguished from a passive process occurring with profound cell damage, e.g., necrosis or apoptosis, and has been elucidated as an active process in monocytes and macrophages after pro-inflammatory stimulation with LPS, IFN-c, TNFa or IL-1b. ‘‘Outside’’ cells, HMGB-1 serves as an inflammatory mediator affecting synthesis of TNFa, monocyte chemotactic protein (MCP)-1 and expression of cell adhesion molecules ICAM-1 and VCAM-1 [2]. A recent publication by Oyama et al. [3] sheds light on the potent role of HMGB-1 in an experimental nephritis model caused by adenine excess. Adenine-rich diet (2,8-dihydroxyadenine (DHA)induced nephritis) provokes interstitial nephritis [3]. Oyama and colleagues set up the hypothesis that activated infiltrating macrophages, which are abundantly found in renal granulomas, may release HMGB-1 and thereby perpetuate disease, e.g., by enhancing MCP-1 expression and secretion. Furthermore, the study addressed the question whether secreted MCP-1 may attract more macrophages, which also release HMGB-1. Thus, the authors postulated the existence of a dangerous self-amplifying vicious circle in the interstitial nephritis model [3]. As a result, Oyama et al. demonstrate elevated levels of HMGB-1 and MCP-1 in renal tissue, urine and serum samples of adenine-fed rats. Moreover, receptors of extracellular HMGB-1, i.e., receptor for advanced glycation end products (RAGE) and tolllike receptor-4 (TLR4), were up-regulated in kidney tissue from rats fed with adenine. Intraperitoneal injection of HMGB-1 in the course of adenineinduced nephritis resulted in functional impairment, as indicated by enhanced serum blood urea nitrogen (BUN) and creatinine levels. When HMGB-1?/mice were investigated in the same disease model, MCP-1 expression was reduced, and accumulation of macrophages in the kidneys was decreased. In vitro, renal tubular epithelial cells were found to enhance MCP-1 secretion upon HMGB-1 stimulation. V. Shpacovitch P. R. Mertens (&) Nephrology and Hypertension & Endocrinology and Metabolic Diseases, Otto-von-Guericke University Magdeburg, Leipziger Str. 40, 39120 Magdeburg, Germany e-mail: peter.mertens@med.ovgu.de