Amelioration of experimental autoimmune encephalomyelitis by in vivo reprogramming of macrophages using pro-resolving factors.

BACKGROUND: Reinstating inflammation resolution represents an innovative concept to regain inflammation control in diseases marked by chronic inflammation. While most therapeutics target inflammatory molecules and inflammatory effector cells and mediators, targeting macrophages to initiate inflammation resolution to control neuroinflammation has not yet been attempted. Resolution-phase macrophages are critical in the resolution process to regain tissue homeostasis, and are programmed through the presence and elimination of apoptotic leukocytes. Hence, inducing resolution-phase macrophages might represent an innovative therapeutic approach to control and terminate dysregulated neuroinflammation. METHODS: Here, we investigated if the factors released by in vitro induced resolution-phase macrophages (their secretome) are able to therapeutically reprogram macrophages to control neuroinflammation in the model of experimental autoimmune encephalomyelitis (EAE). RESULTS: We found that injection of the pro-resolutive secretome reduced demyelination and decreased inflammatory cell infiltration in the CNS, notably through the in vivo reprogramming of macrophages at the epigenetic level. Adoptive transfer experiments with in vivo or in vitro reprogrammed macrophages using such pro-resolutive secretome confirmed the stability and transferability of this acquired therapeutic activity. CONCLUSIONS: Overall, our data confirm the therapeutic activity of a pro-resolution secretome in the treatment of ongoing CNS inflammation, via the epigenetic reprogramming of macrophages and open with that a new therapeutic avenue for diseases marked by neuroinflammation.

Comparison of procedure times and collection efficiencies using integrated and multistep nonintegrated procedures for extracorporeal photopheresis.

BACKGROUND: Extracorporeal photopheresis (ECP) is a blood-based therapeutic procedure increasingly used for modulation of immune dysregulation in various underlying disease settings. The aim of this study was to compare the procedure times and blood collection efficiencies between the two approaches currently utilized in European centers: the integrated versus the multistep nonintegrated procedures. METHODS: A retrospective data analysis was conducted, comparing treatment data from patients who received ECP therapy at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken GmbH, where the integrated and multistep nonintegrated procedures are routinely used in an approximated setup. RESULTS: During the observation period, a total of 15 patients who were treated with alternating systems on 2 consecutive days were identified. This allowed treatment pair comparisons with minimal interpatient variabilities, similar to a cross-over design even though analyzed retrospectively. Total average procedure times with the integrated system were 99.3 vs 122.0 minutes with the multistep nonintegrated procedures, respectively. Significant differences were observed for all steps of the ECP procedure: (a) time for buffy coat collection, 66.5 vs 74.7; (b) handling/transfer, 2.8 vs 18.7; (c) irradiation, 20.3 vs 11.7; and (d) reinfusion/handling time, 9.6 vs 16.3 minutes. The calculated collection throughput was 7.79 mL/min for the integrated and 7.84 mL/min for the multistep nonintegrated procedures, and with a white blood cell (WBC) collection efficiency of 34.2% and 21.0%, respectively. CONCLUSION: The data presented in this study show a significant shorter overall procedure time and higher WBC collection efficiency for the integrated ECP system.