Introduction: PQA-18 (Prenylated quinolinecarboxylic acid compound 18) has been reported as a novel immunosuppressant that attenuates various cytokine productions, such as IL-2 & TNF-a, and differentiation of macrophages by inhibiting PAK2 inhibitor. In this study, we investigated this drug function mainly on macrophages using the rat small intestinal transplant model.

Methods: Male Dark Agouti (DA) (RT-1a) and Lewis (RT-1l) rats, 7 to 9 weeks old, were used as donor and recipient, respectively. An approximately 15 cm ileal grafts from the donor was heterotopically transplanted to the recipient rats. A Thirty-Vella loop was placed in the right abdominal flank. The recipient rat was treated with PQA-18 (4 mg/kg/per day) by intraperitoneal injection (ip) from postoperative day 1 (POD1)　to two weeks. The control group, without PQA-18, was treated with just the same amount of Dimethyl sulfoxide (DMSO), the solvent for PQA-18. We firstly compared with graft survival of both groups. The rejection was manifested by progressive stoma coloring from ischemia and necrosis and the development of an abdominal mass, based on our previous study. Next, total cells from intestinal mesenteric lymph nodes (MLN) and graft Payer’s patch (PP) were collected on POD6 and the number of macrophages was investigated using FACS cell analyzer.

Results: The graft survival was significantly prolonged by PQA-18 injection. While the survival time was 7.0 ± 0.77 days in the control group (n=9), the PQA group showed 10.7 ± 1.26 days’ survival (n=10) (p<0.001).

The number of macrophages was also significantly reduced to 9.62 ± 1.22 % in MLN of the PQA group, while the number was 22.05 ± 2.00 % (p=0.004) in the control group. In addition, the number of infiltrated macrophages in PP was18.72 ± 2.33% in the control group, whereas the PQA-18 group indicated 6.55 ± 1.26% (p=0.007). The infiltration of macrophage was significantly suppressed in the PQA group.

Conclusion: PQA-18 significantly provided the prolongation of the graft survival in the rat small intestine transplantation model, together with the inhibited number of macrophages in the graft MLN & PP. It was suggested that PQA-18 has the suppressive effect not only on the differentiation but infiltration of macrophages. Further studies of the effect of this drug on macrophages are undergoing.