Recently, Wewering et al. (2017) from the Department of Chemical and Product Safety in Berlin have published a study about a co-culture system that aims to simulate hepatocyte–macrophage interactions. It is well established that complex interactions between hepatocytes and non-parenchymal cells take place during induction of liver toxicity (Baeck and Tacke 2014; Hammad et al. 2014; Hoehme et al. 2010). Particularly, neutrophilic granulocytes and macrophages have been reported to aggravate the damage induced by hepatotoxic compounds (Adams et al. 2010; Jaeschke et al. 2012; Marques et al. 2012, 2015; Dong et al. 2007). Nevertheless, current in vitro testing for hepatotoxicity mostly relies on hepatocyte cultures without addition of immune cells (Grinberg et al. 2014; Valente et al. 2016; Arbo et al. 2016; Deharde et al. 2016; Ghallab et al. 2016; Ramboer et al. 2015; Godoy et al. 2016; Hammad et al. 2015). Currently, it remains unclear whether co-cultures of hepatocytes with immune cells really improve hepatotoxicity testing. One challenge studying this task is to avoid spontaneous activation of immune cells in vitro. To gain more insight into hepatocyte–immune cell interactions, Wewering et al. (2017) compared cultures of HepG2 cells alone to co-cultures of HepG2 cells and the macrophage cell line THP-1.

Interestingly, the hepatotoxic compound ketoconazole induced secretion of the pro-inflammatory cytokines CXCL8, TNF-α and CCL3 only in the co-culture system but not in HepG2 mono-cultures. The study presents clear evidence that co-cultures of immune cells and hepatocytes may indeed improve in vitro hepatotoxicity testing. Limitations of the current study are that so far only one compound has been tested and that no primary cells could be used. Nevertheless, the study of Wewering et al. is of high interest and further studies are needed to gain deeper insight as to which degree hepatocyte–immune cell interactions can be simulated in vitro.