Experimental animal models show beneficial effects of administration of mesenchymal stem cells (MSC) on ischemia-reperfusion injury and survival of organ transplants. The immunomodulatory responses that are induced by MSC are, however, unknown. We showed that intravenously infused C57BL/6-GFP MSC home to the lungs in C57BL/6 recipient mice and induce an inflammatory response. This response was characterized by increased mRNA expression of monocyte chemo-attractant protein-1 (MCP1), IL1-b and TNF-a in lung tissue 2h after MSC infusion. Expression levels returned to normal after 20h. Following the same timeline, serum levels of pro-inflammatory IL6, CXCL1 and MCP1 protein increased, demonstrating systemic immune activation after MSC infusion. In liver tissue, where no C57BL/6-GFP MSC were detected, MCP1 and TNF-a mRNA levels peaked 4h after MSC infusion, while IFN-g peaked at 3 days. The expression of the anti-inflammatory cytokines TGF-b, IL4 and IL10 was only marginally affected by MSC infusion. Nevertheless, 3 days after MSC infusion animals developed a milder inflammatory response to LPS. Our results suggest that the immunomodulatory effects of MSC originate from an initial inflammatory response, which is followed by a phase of reduced immune reactivity. Understanding the immunomodulatory mechanisms of MSC treatment will contribute to the development of effective immune therapy with MSC.

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