INCREASED EXPRESSION OF TISSUE CYTOKINES IN GRAFT-VERSUS-HOST DISEASEAFTER SMALL-BOWEL TRANSPLANTATION IN THE RAT

Background. Graft-versus-host disease (GVHD) occurs in the recipient a fter small bowel transplantation (SET). Proinflammatory cytokines, suc h as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-ga mma), and interleukin 6 (IL-6), may be important mediators of GVHD, In creased expression of these cytokines might precede the clinical manif estations of GVHD induced by SET. Methods. Heterotopic SET was perform ed using Lewis donors into Lewis x Brown Norway F1 (LBN-F1) recipients . The isograft control was performed from LBN-F1 into LBN-F1. Animals were killed on the 5th and 11th postoperative day (POD). mRNA was isol ated from recipient native small bowel, colon, spleen, liver, and mese nteric lymph nodes and from nonsurgical controls as baseline, Semiquan titative reverse transcriptase polymerase chain reaction was performed to amplify mRNA transcripts for TNF-alpha, IFN-gamma, and IL-6 using alpha(32)P-dATP incorporation, Clinical signs, histologic assessment, and cytokine expression were correlated. Results. On POD 5, there were neither clinical signs nor histologic features of GVHD, but mRNA expr ession of TNF-alpha and IL-6 in small bowel, IL-6 in spleen, and IFN-g amma in mesenteric lymph nodes were significantly increased in allogra ft animals when compared with normal and isograft tissues. On POD 11, both the clinical signs and histologic features of GVHD were seen, and TNF-alpha and IL-6 in native small bowel, TNF-alpha in colon, IFN-gam ma in spleen, and IL-6 in mesenteric lymph nodes were significantly in creased in allograft animals when compared with that in normal and iso graft tissues. Conclusions. In conclusion, TNF-alpha, IFN-gamma, and I L-6 expression precede clinical onset and histologic evidence of GVHD in specific tissues. Therefore, increased expression of these cytokine s is correlated with the development of GVHD in this model of SET.