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Acute kidney injury (AKI) is a significant complication of cardiac surgery and is associated with increased morbidity and mortality [1]. Despite much research, there is no specific therapy available. Although AKI can be multifactorial, ischaemia reperfusion injury (IRI) often plays a key role. Thus, cardiac surgery offers an attractive opportunity for translational AKI research given the predictive haemodynamic challenge to renal perfusion. Hemeoxygenase-1 (HO-1) is a key inducible anti-inflammatory enzyme that catalyses the breakdown of the pro-oxidant protein heme ubiquitously found at inflamed sites. The drug heme arginate has been in use for over 20 years in the treatment of porphyria but also upregulates HO-1 in peripheral blood mononuclear cells (PBMCs) [2] and ameliorates calf muscle ischaemia [3]. In addition, treatment of mice with heme arginate prior to renal IRI strongly upregulates renal HO-1 expression and protects from AKI [4]. We therefore hypothesise that HA may offer a prophylactic therapy for human renal IRI via the upregulation of HO-1.

Macrophages function as sentinel, cell-regulatory hubs capable of initiating, perpetuating and contributing to the resolution of an inflammatory response, following their activation from a resting state. Highly complex and varied gene expression programs within the macrophage enable such functional diversity. To investigate how programs of gene expression relate to the phenotypic attributes of the macrophage, the development of in silico modeling methods is needed. Such models need to cover multiple scales, from molecular pathways in cell-autonomous immunity and intercellular communication pathways in tissue inflammation to whole organism response pathways in systemic disease. Here, we highlight the potential of in silico macrophage modeling as an amenable and important yet under-exploited tool in aiding in our understanding of the immune inflammatory response. We also discuss how in silico macrophage modeling can help in future therapeutic strategies for modulating both the acute protective effects of inflammation (such as host defense and tissue repair) and the harmful chronic effects (such as autoimmune diseases)., 7 pages plus 1 figure