Predominant Inflammatory and Th1 biased cytokine secretion pre- and post- kidney transplantation

Abstract

Abstract. A key goal in post-transplant monitoring is the diagnostic detection of harmful processes in the allograft early which can be easily and non-invasively assessed. Cytokines are crucial mediators involved in immune responses leading to rejection. It is known that episodes of viral infections and acute rejection can cause an increase in pro-inflammatory cytokines in transplant recipients. This study is significant since detailed analysis of cytokines was performed in kidney transplant patients pre- and post-transplant to assess the impact of graft implantation. Twenty patients with mean age of 35 years and comprising 8 females who underwent renal transplantation were included in the study.  The mean follow-up time for the study cohort was 5 months. Using a multiplex microassay, twelve cytokines [IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, granulocyte–macrophage colony-stimulating factor, IFN-g and tumour necrosis factor] were measured simultaneously before and after transplant. A strong pro-inflammatory response was seen as the levels of circulating IL-1b (p<0.02) and IL-6 (p<0.01) increased post-transplant.  A Th1 bias was due to increased IFNg (p<0.05) and absent IL-4 and IL-10 post-transplant. Levels of IL-1a, IL-2, IL-7, IL-12, GM-CSF and TNFa remained low and unchanged whilst IL-8 levels was reduced (p<0.02). These findings show a strong pro-inflammatory response with a Th1 cytokine bias and this immunological outcome places the patient at risk of graft rejection. We suggest that diagnostic parameters such as cytokines can be used to monitor allografts non-invasively and may have the potential to guide clinical decisions regarding immunosuppressive therapy which could improve outcomes post-transplantation.

 

Key words:   Kidney transplant, allograft rejection, cytokines, Th1 bias

Keywords

• Kidney transplant, allograft rejection, cytokines, Th1 bias

Kaynakça

1. 1. Sadeghi M, Daniel V, Weimer R, et al. Pretransplant Th1 and post-transplant Th2 cytokine patterns are associated with early acute rejection in renal transplant recipients. Clin Transplant 2003; 17: 151-157.
2. 2. D'Elios MM, Josien R, Manghetti M, et al. Predominant Th1 cell infiltration in acute rejection episodes of human kidney grafts. Kidney Int 1997; 51: 1876-1884.
3. 3. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 2006; 8: 2.
4. 4. Jones SA. Directing transition from innate to acquired immunity: defining a role for IL-6. J Immunol 2005; 175: 3463-3468.
5. 5. Korn T, Oukka M, Kuchroo V, Bettelli E. Th17 cells: effector T cells with inflammatory properties. Semin Immunol 2007; 19: 362-371.
6. 6. Kumar G, Usha S, Singh RG. Evaluation of serum tumor necrosis factor α and its correlation with histology in chronic kidney disease, stable renal transplant and rejection cases. Saudi J Kidney Dis Transpl 2009; 20: 1000-1004.
7. 7. Nickerson P. Post-transplant monitoring of renal allografts: are we there yet? Curr Opin Immunol 2009; 21: 563-568.
8. 8. Hoffmann SC, Hale DA, Kleiner DE, et al. Functionally significant renal allograft rejection is defined by transcriptional criteria. Am J Transplant 2005; 5: 573-581.

9. 9. Renesto PG, Ponciano VC, Cenedeze MA, Saraiva Câmara NO, Pacheco-Silva A. High expression of Tim-3 mRNA in urinary cells from kidney transplant recipients with acute rejection. Am J Transplant 2007; 7: 1661-1665.
10. 10. Penix LA, Sweetser MT, Weaver WM, et al. The proximal regulatory element of the interferongamma promoter mediates selective expression in T cells. J Biol Chem 1996; 271: 31964-31972.
11. 11. White GP, Watt PM, Holt BJ, Holt PG. Differential patterns of methylation of the IFNgamma promoter at CpG and non-CpG sites underlie differences in IFN-gamma gene expression between human neonatal and adult CD45RO- T cells. J Immunol 2002; 168: 2820- 2827.
12. 12. De Larco JE, Wuertz BR, Yee D, Rickert BL, Furcht LT. Atypical methylation of the interleukin-8 gene correlates strongly with the metastatic potential of breast carcinoma cells. Proc Natl Acad Sci USA 2003; 100: 13988-13993.
13. 13. Dinavahi R, Heeger PS. T-cell immune monitoring in organ transplantation. Curr Opin Organ Transplant 2008; 13: 419-424.