The Molecular Influence of Graphene and Graphene Oxide on the Immune System Under In Vitro and In Vivo Conditions.

Graphene and graphene oxide (GO), due to their physicochemical properties and biocompatibility, can be used as an innovative biomedical material in biodetection, drug distribution in the body, treating neoplasms, regenerative medicine, and in implant surgery. Research on the biomedical use of graphene and GO that has been carried out until now is very promising and shows that carbon nanomaterials present high biocompatibility. However, the intolerance of the immune system to graphene nanomaterials, however low, may in consequence make it impossible to use them in medicine. This paper shows the specific mechanism of the molecular influence of graphene and GO on macrophages and lymphocytes under in vitro and in vivo conditions and their practical application in medicine. Under in vitro conditions graphene and GO cause an increased production of pro-inflammatory cytokines, mainly IL-1, IL-6, IL-10 and TNF-α, as a result of the activation of Toll-like receptors in macrophages. Graphene activates apoptosis in macrophages through the TGFbr/Smad/Bcl-2 pathway and also through JNK kinases that are stimulated by an increase of ROS in the cell or through a signal received by Smad proteins. Under in vivo conditions, graphene nanomaterials induce the development of the local inflammatory reaction and the development of granulomas in parenchymal organs. However, there is a huge discrepancy between the results obtained by different research groups, which requires a detailed analysis. In this work we decided to collect and analyze existing research and tried to explain the discrepancies. Understanding the precise mechanism of how this nanomaterial influences immune system cells allows estimating the potential influence of grapheme and GO on the human body.