Cytokine and chemokine expression kinetics after corneal transplantation

Background. Allogeneic rejection is the most common cause of corneal graft failure. The aim of this work was to establish the kinetics of cytokine and chemokine mRNA expression before and after onset of corneal graft rejectio n. Methods. Intracorneal cytokine and chemokine mRNA levels were investigated in the Brown Norway-->Lewis inbred rat model in which rejection onset is ob served at 8/9 days after grafting in all animals. Nongrafted corneas and sy ngeneic (Lewis-->Lewis) corneal transplants were used as controls. Donor an d recipient cornea was examined by quantitative competitive reverse transcr iption-polymerase chain reaction (RT-PCR) for hypoxyanthine phosphoribosylt ransferase (HPRT), CD3, CD25, interleukin (IL)-1 beta, IL-1RA, IL-2, IL-6, IL-10, interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), transform ing growth factor (TGF)-beta1, and macrophage inflammatory protein (MIP)-II and by nonquantitative RT-PCR for IL-4, IL-5, IL-12 p40, IL-13, TGF-beta2, monocyte chemotactic protein-1 (MCP-1), MIP-1 alpha, MIP-1 beta, and RANTE S (for regulated upon activation normal T cell expressed and secreted), Results. A biphasic expression of cytokine and chemokine mRNA was found aft er transplantation. During the early phase (days 3-9), there was an elevati on of the majority of the cytokines examined, including IL-1 beta, IL-6, IL -10, IL-12 p40, and MIP-II. There was no difference in cytokine expression patterns between allogeneic or syngeneic recipients at this time. In syngen eic recipients, cytokine levels reduced to pretransplant levels by day 13, whereas levels of all cytokines rose after observed rejection onset in the allografts, including TGF-beta1, TGF-beta2, and IL-1RA. The T cell-derived cytokines IL-4, IL-13, and IFN-gamma were detected only during the rejectio n phase in allogeneic recipients. Conclusions. There is an early cytokine and chemokine response to the trans plantation process, evident in syngeneic and allogeneic grafts, that probab ly drives angiogenesis, leukocyte recruitment, and affects leukocyte functi ons. After an immune response has been generated, allogeneic rejection resu lts in the expression of Th1 cytokines (IL-2, IL-12 p40, IFN-gamma), Th2 cy tokines (IL-4, IL-6, IL-10, and IL-13), and anti-inflammatory/Th3 cytokines (TGF-beta1/2 and IL-1RA).