IL-10/Fc INHIBITS MACROPHAGE FUNCTION AND PROLONGS PANCREATIC ISLET XENOGRAFT SURVIVAL1

Abstract

IL-10/Fc prolonged rat pancreatic islet xenograft survival by inhibiting macrophage mediated immune responses. The effectiveness of this agent when administered pretransplant suggests it may have a role as an induction agent with potential clinical application.

Survival of mitomycin C-treated pancreatic islet xenografts is mediated by increased expression of transforming growth factor-β1

“…Infiltration of neutrophils and B cells tended to be inhibited, although the level was not statistically significant. These results are consistent with the previous findings of Feng et al (20) showing that ultimate rejection of the xenografts appears to be mediated by a CD4 ϩ T-cell-dependent mechanism probably caused by inadequate inhibition of IL-12 production by macrophages. In our model, CD8 ϩ cells were also inhibited, although these cells could not be the effector cells when CD4 ϩ cells are spared (21).…”

Human Pancreatic Islets Produce and Secrete MCP-1/CCL2: Relevance in Human Islet Transplantation

“…Patients' characteristics are detailed in Tables 1 and 2. To reach the minimum number of 5,000 IE/kg body wt, 6 of the 14 patients received two islet preparations, either within 10 days from the first preparation (30,33,34,38,40) or 4 months later (41). Starting from the second month after transplant, insulin requirement reduction correlates inversely with the MCP-1 secretion capacity of islets (Fig.…”

“…In the early days after transplantation, the islets suffer hypoxia and inflammatory response to the graft, which lead to islet dysfunction, apoptosis, and a reduction in ␤-cell mass, followed by tissue remodeling. Macrophages play an important role in early islet graft loss (37)(38)(39)(40)(41), and their depletion by gadolinium or clodronate improved graft survival in a rodent model of islet transplantation (42).…”

Interleukin-10 Therapy—Review of a New Approach

“…Because of its anti-inflammatory properties and its association with regulatory T cells, IL-10 should have some benefit on graft survival. In fact, IL-10 inhibits ischemia/reperfusion injury (Deng et al, 2001), prolongs allograft survival (Feng et al, 1999;Zuo et al, 2001), and is essential for the action of regulatory T cells mediating tolerance at least in some transplant models (Hara et al, 2001). In addition, IL-10 prevents several side effects of OKT3 mAb-mediated cytokine release (Moore et al, 2001).…”