Early changes in IL-21, IL-22, CCL2 and CCL4 serum cytokines after outpatient autologous transplantation for multiple sclerosis: A proof of concept study.

Changes in serum cytokines after autologous hematopoietic stem cell transplantation (AHSCT) in multiple sclerosis (MS) patients were documented. Thirty-six consecutive MS patients who had their Expanded Disability Status Scale (EDSS) scored before AHSCT were prospectively enrolled. Cyclophosphamide (Cy) was infused at 200 mg/Kg in two administrations given 10 days apart; the first dose for mobilization, the second as the conditioning regimen. Patients were mobilized with 10 µg/kg/day subcutaneous G-CSF. Serum was collected 14 days before and 14 after AHSCT. IL-6, IL-9, IL -10, IL 17-A, IL-21, IL-22, IL-23, TNF-A, CCL2, CCL3 and CCL4 were measured by magnetic bead-based immunoassay. T-test and Wilcoxon test were used to compare cytokine levels before and after AHSCT. There were 28 women and 8 men with a median age of 46 (15-62) years, median duration of MS was 9.5 (1-32) years, EDSS score was 5.7 (1.5-8.0). Patients had a decrement of pro-inflammatory IL-21 and IL-22 (p= 0.003 and p= 0.028), and an increment of anti-inflammatory CCL2 and CCL4 (p<0.001 and p= 0.039) after AHSCT. Decrease of IL-21 and IL-22 coupled with an increment of CCL2 and CCL4 could reflect the immunomodulatory effect of auto-HSCT and be an early indicator of its efficacy.