Acute Systemic Profiles of Inflammation and Coagulation Following Autologous Islet Transplantation

Abstract

Introduction: Prevention of early graft loss is a major issue in improving clinical outcomes of allogeneic as well as autologous islet transplantation. The instant blood mediated inflammatory reaction (IBMIR) has been well investigated in allogeneic islet transplant setting; however, inflammatory or coagulatory responses in autologous islet transplantation (AIT) have not been clearly documented. We focused on systemic inflammatory and coagulatory responses in early phase of clinical AIT. Methods: A total of ten consecutive patients with refractory chronic pancreatitis who underwent AIT at our institute were included in this study. Serum C-peptide, inflammatory and coagulation factors were measured at the following time points: prior, middle and end of islet infusion as well as 15 min, 1 hour, 3 hours, 6 hours and 24 hours after the IAT. Serum C-peptide response during islet infusion was considered as a surrogate maker of early islet destruction and the patients with the early C-peptide response over or less than 1000 pmol/L were grouped as high- or low-damage groups, respectively. Peak values of cytokine and coagulation factors within 24 hours after AIT were compared between the two groups using Mann-Whitney U test non-parametrically. Results: No significant differences were found in patient characteristics and transplant condition except for body mass index (p=0.04, Table 1)[Table 1. Patient and transplant characteristics]Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, interferon γ-induced protein (IP)-10/CXCL10, monocyte chemotactic protein (MCP)-1/CCL2, interferon (IFN)-γ, thrombin-antithrombin complex (TAT), complement 3a (C3a) were significantly elevated within 24 hours after AIT compared to the prior infusion levels (p with nonparametric matched Wilcoxon signed-rank test < 0.01). Among these factors, significant differences were found in TNF-α and C3a levels between the two group (p < 0.05) while IP-10 had marginally significant difference (p = 0.06).[Fig. 1. Elevated inflammatory/coagulatory factors]Conclusions: Systemic inflammatory and coagulatory responses were observed in in early phase of AIT for the patients with chronic pancreatitis. Greater islet graft damage may be associated with higher release of inflammatory/coagulatory factors, suggesting that inhibition of these factors could enhance islet engraftment in AIT. The impact of IBMIR should be validated in large scale clinical studies on AIT.