| First Author | Wyburn K | Year | 2006 |
| Journal | Am J Transplant | Volume | 6 |
| Issue | 11 | Pages | 2612-21 |
| PubMed ID | 17049054 | Mgi Jnum | J:135970 |
| Mgi Id | MGI:3794853 | Doi | 10.1111/j.1600-6143.2006.01536.x |
| Citation | Wyburn K, et al. (2006) Interleukin-18 affects local cytokine expression but does not impact on the development of kidney allograft rejection. Am J Transplant 6(11):2612-21 |
| abstractText | Interleukin-18 is predominantly a macrophage-derived cytokine with a key role in inflammation and cell-mediated immunity. Having previously demonstrated IL-18 upregulation in a rat model of kidney rejection, here we examined IL-18 in a fully MHC-mismatched murine model of acute kidney rejection using IL-18-deficient recipients (IL-18-/-) and animals administered neutralizing IL-18 binding protein (IL-18BP). Gene expression of IL-18 and its receptor were significantly upregulated in allografts compared to isografts, as was the cellular infiltrate (T cells and macrophages) (p < 0.001). Allografts developed kidney dysfunction (p < 0.05) and tubulitis (p < 0.01) not observed in controls. There was a significant reduction in gene expression of IL-18 downstream pro-inflammatory molecules (iNOS, TNFalpha and IFNgamma) in IL-18-/- recipients (p < 0.01), and IL-18BP-treated animals. The CD4+ infiltrate and IL-4 mRNA expression was greater in the IL-18-/- recipients than wild-type (WT) allografts and IL-18BP-treated animals (p < 0.05), suggesting a Th2-bias which was supported by IFNgamma and IL-4 ELISPOT data and an increased eosinophil accumulation (p < 0.001). Neither IL-18 deficiency nor neutralization prevented renal dysfunction or tubulitis. This study demonstrates increased production of IL-18 in murine kidney allograft rejection and provides evidence that IL-18-induced pathways of inflammation are active. However, neither IL-18 deficiency nor neutralization was protective against the development of allograft rejection. |
