CHANGES IN LIVER-GLYCOGEN AND LIPID-METABOLISM DURING TRANSIENT GRAFT-VERSUS-HOST (GVH) AND GRAFT-VERSUS-LEUKEMIA (GVL) REACTIVITY

We investigated the influence of transient graft-versus-leukemia (GvL) and graft-versus-host reactivity (GvH) following allogeneic immune ce ll transfer on the glycogen and lipid metabolism in the liver of affec ted mice to better understand the underlying mechanism of these phenom ena. As model we used a well established adoptive cellular immunothera py (ADI) system. This involves transfer of in situ activated anti-tumo r immune spleen lymphocytes (ISPL) from the tumor-resistant mouse stra in B10.D2 (H-2(d), M1s(b)) into 5 Gy sublethally irradiated syngeneic ESb-MP lymphoma-bearing DBA/2 (H-2(d), M1s(a)) mice. Experiments were performed by transfer of ISPL from B10.D2 into DBA/2 tumor-bearing mic e (GvL effect on liver metabolism) and into DBA/2 non-tumor-bearing mi ce (GvH effect on liver metabolism). Our results show that glycogen in hepatocytes decreased dramatically 5 days after ISPL transfer, which coincided with a high increase of large fat granules. 8 days after ISP L transfer, livers started to re-express glycogen and to decrease thei r lipid content. Normalization of both parameters was seen after day 3 0. These changes were qualitatively similar in both GvL and GvH. Measu rement of activity of the liver marker enzymes, GOT and GPT, in the se ra of animals subjected to GvL or GvH, showed peak values also at day 5, coinciding with the loss of glycogen. Quantitative differences were seen, however, in that much higher levels were reached in GvL than in GvH. Immune system recovery from irradiation damage and liver regener ation after immune cell mediated liver damage are likely explanations for the reversibility of the metabolic changes and for the lack of GVH disease and mortality in this new and effective cellular cancer immun otherapy model.