ALTERATIONS IN RENAL INTERLEUKIN-L PRODUCTION DURING KIDNEY-TRANSPLANT REJECTION IN THE RAT - THE EFFECTS OF HIGH-DOSE METHYLPREDNISOLONE

To characterize the role of interleukin-1 in renal allograft rejection , we examined the temporal relationship of IL-1 production to changes in renal function and histology in a rat kidney transplantation model. In rat renal allografts, both glomerular filtration rate and renal pl asma flow (RPF) fell progressively from days 4 through 6 following tra nsplantation. The reduction in allograft function was accompanied by h istologic changes consistent with rejection and enhanced steady-state levels of IL-1 beta mRNA measured by Northern blot. This increase in I L-1 beta mRNA levels was associated with a forty-fold increase in IL-1 bioactivity in eluates of kidney allografts compared with isografts. In rejecting allografts, these changes also coincided with increased p roduction of thromboxane B-2 (TxB(2)) by the graft. To attempt to modi fy IL-1 production in the transplanted kidney, a separate group of ani mals with renal allografts were treated with 80 mg/kg/day of methylpre dnisolone for 6 days. GFR in MP-treated animals was significantly pres erved compared with vehicle-treated animals. However, similar histolog ic manifestations of rejection were found in both groups. Although IL- 1 beta mRNA levels in the kidney were not changed with MP treatment, r enal IL-1 bioactivity was reduced four-fold in animals that received M P compared with controls. Thus, IL-1 beta gene expression and IL-1 pro tein production are stimulated in rejecting kidney transplants. MP adm inistration improves allograft function and inhibits IL-1 production, apparently at a post-transcriptional level. We hypothesize that overpr oduction of IL-1 during kidney transplant rejection may promote allogr aft dysfunction and injury. Some of the beneficial effects of corticos teroids in acute rejection may be mediated through inhibition of IL-1 release within the allograft.