Based on previous pre-clinical work within the Research Unit 2165, Winkler and Geißler will use a first-in-men clinical phase I/IIa study to unravel the details of immune-modulation: Promoting humeral head fracture healing by local immunomodulation in a prospective, mono-centre, randomised, open labelled, controlled study, the prostacyclin analogue Iloprost will be used to locally dampen CD8+ effector T cell activity and simultaneously increase CD4+ regulatory T cell levels via the modulation of the cyclic AMP/protein kinase A (cAMP/PKA) pathway. Local Iloprost administration in a mouse osteotomy model resulted in reduced CD8+ T cell levels and reduced pro-inflammatory cytokine secretion at the site of injury and significantly improved bone healing. Shaping the local inflammatory response is a suitable and safe approach to improve human bone regeneration especially in elderly patients with an experienced immune system. In a prospective, randomised phase I/IIa study safety and efficacy of a local Iloprost administration will be assessed in patients suffering from proximal humeral head fractures which have a high non-union rate. Winkler and Geißler also aim to characterise the patients’ immune experience to gain a more mechanistic understanding of how the bone repair process is altered by local cAMP/PKA pathway modulation and to determine the direct or indirect effects of the immunomodulation on bone tissue and its function.