SummaryVolatile anaesthetics such as sevoflurane attenuate inflammatory processes, thereby impacting patient outcome significantly. Their inhalative administration is, however, strictly limited to controlled environments such as operating theatres, and thus an intravenously injectable immunomodulatory drug would offer distinct advantages. As protective effects of volatile anaesthetics have been associated with the presence of trifluorinated carbon groups in their basic structure, in this study we investigated the water-soluble sevoflurane metabolite hexafluoro-2-propanol (HFIP) as a potential immunomodulatory drug in a rat model of endotoxic shock. Male Wistar rats were subjected to intravenous lipopolysaccharide (LPS) and thereafter were treated with HFIP. Plasma and tissue inflammatory mediators, neutrophil invasion, tissue damage and haemodynamic stability were the dedicated endpoints. In an endotoxin-induced endothelial cell injury model, underlying mechanisms were elucidated using gene expression and gene reporter analyses. HFIP reduced the systemic inflammatory response significantly and decreased endotoxin-induced tissue damage. Additionally, the LPS-provoked drop in blood pressure of animals was resolved by HFIP treatment. Pathway analysis revealed that the observed attenuation of the inflammatory process was associated with reduced nuclear factor kappa B (NF-jB) activation and suppression of its dependent transcripts. Taken together, intravenous administration of HFIP exerts promising immunomodulatory effects in endotoxaemic rats. The possibility of intravenous administration would overcome limitations of volatile anaesthetics, and thus HFIP might therefore represent an interesting future drug candidate for states of severe inflammation.

In the past, our research group was able to successfully remove circulating tumor cells with magnetic nanoparticles. While these cancer cells are typically present in low numbers, we hypothesized that magnetic nanoparticles, besides catching single cells, are also capable of eliminating a large number of tumor cells from the blood ex vivo. This approach was tested in a small pilot study in blood samples of patients suffering from chronic lymphocytic leukemia (CLL), a mature B-cell neoplasm. Cluster of differentiation (CD) 52 is a ubiquitously expressed surface antigen on mature lymphocytes. Alemtuzumab (MabCampath®) is a humanized, IgG1κ, monoclonal antibody directed against CD52, which was formerly clinically approved for treating chronic lymphocytic leukemia (CLL) and therefore regarded as an ideal candidate for further tests to develop new treatment options. Alemtuzumab was bound onto carbon-coated cobalt nanoparticles. The particles were added to blood samples of CLL patients and finally removed, ideally with bound B lymphocytes, using a magnetic column. Flow cytometry quantified lymphocyte counts before, after the first, and after the second flow across the column. A mixed effects analysis was performed to evaluate removal efficiency. p < 0.05 was defined as significant. In the first patient cohort (n = 10), using a fixed nanoparticle concentration, CD19-positive B lymphocytes were reduced by 38% and by 53% after the first and the second purification steps (p = 0.002 and p = 0.005), respectively. In a second patient cohort (n = 11), the nanoparticle concentration was increased, and CD19-positive B lymphocytes were reduced by 44% (p < 0.001) with no further removal after the second purification step. In patients with a high lymphocyte count (>20 G/L), an improved efficiency of approximately 20% was observed using higher nanoparticle concentrations. A 40 to 50% reduction of B lymphocyte count using alemtuzumab-coupled carbon-coated cobalt nanoparticles is feasible, also in patients with a high lymphocyte count. A second purification step did not further increase removal. This proof-of-concept study demonstrates that such particles allow for the targeted extraction of larger amounts of cellular blood components and might offer new treatment options in the far future.