Reduktion der immunologischen Abstoßungsreaktion in Composite Tissue Allotransplantation durch Hitzeschock-Präkonditionierung

BACKGROUND: In spite of great advances in the field of composite tissue allotransplantations (CTA), there is still a major need for optimisation in terms of immunosuppression. Heat shock proteins are produced as a reaction of the body during a stress situation. Once elevated, they protect against a second stress and reduce ischaemia-reperfusion injury within transplantations. In the literature the effect of heat shock and HSP70 on rejection after CTA has not been described. The purpose of this experimental study was to examine the effect of heat shock proteins on rejection in a rat model of CTA. Evaluated was the effect of preconditioning by prior heat stress. METHODS AND MATERIALS: Brown Norway rats were systemically heated to a core temperature of 42 °C in order to up-regulate HSP70. The expression of HSP70 in muscle was measured by Western blot analysis and showed a peak 24 h after heat shock. Allogeneic hindlimb transplantations were performed between Brown Norway rats (donor) and Lewis rats (recipients). Group 1 (n=12) was preheated 24 h prior to transplantation. In group 2 (n=12) the transplantation was performed without prior heat shock. Group 3 (n=6) was used as a control group with syngeneic hindlimb transplantations between Lewis rats. Postoperatively the appearance of the transplanted hindlimb was evaluated every 12 h. The beginning of rejection was defined when plantar erythema and foot oedema could be observed at the same time. To verify these discrete signs of rejection, the observation was continued for a further 24 h. In this time erythema and oedema spread over the whole transplanted hindlimb. The rat was sacrificed after specimens of skin and muscle had been taken for histological assessment. RESULTS: The rejection in group 1 (with preconditioning heat shock) began after 4.83±0.44 days, in group 2 (without heat shock) already after 3.88±0.53 days. The difference between these groups was significant because of the small standard deviation (Whitney-Mann U test: p<0.01). CONCLUSION: In our model of allogeneic composite tissue transplantation, a heat shock and subsequent up-regulation of HSP70 led to a significant delay of the immunological rejection. As the graft rejection is an important item influencing the outcome of allogeneic transplantations, these results represent an option to improve the final functional outcome of composite tissue allotransplantations.