13. Cockcroft SW, Gault HM. Prediction of creatinine clearances from serum creatinine. Nephron 1976; 16: 31. 14. Ringden O. Cyclosporine in allogeneic bone marrow transplantation. Transplantation 1986; 42: 445. 15. Yee GC. Pharmacokinetic and pharmacodynamic studies of cyclosporine in bone marrow transplantation. Transplant Proc 1990; 22: 1327. 16. Parikh CR, McSweeney PA, Korular D, et al. Renal dysfunction in allogeneic hematopoietic cell transplantation. Kidney Int 2002; 62: 566. 17. Hows JM, Chipping PM, Fairhead S, et al. Nephrotoxicity in bone marrow transplant recipients treated with cyclosporine A. Br J Haematol 1983; 54: 69. 18. Atkinson K, Downs K, Ashby M, et al. Clinical correlations with cyclospor- ine blood levels after allogeneic bone marrow transplantation: an anal- ysis of four different assays. Transplant Proc 1990; 22: 1331. 19. Aguilara S, Deray G, Desjobert H, et al. Effects of cyclosporine on tubular acidification function in patients with idiopathic uveitis. Am J Nephrol 1992; 12: 425. 20. Woo M, Przepiorka D, Ippoliti J, et al. Toxicities of tacrolimus and cyclo- sporine A after allogeneic blood stem cell transplantation. Bone Marrow Transplant 1997; 20: 1095. 21. Wingo CS, Weiner ID. Disturbances in control of body fluid volume and composition disorders of K + balance. In: Brenner BM, Rector S. The Kidney [6th ed]. Philadelphia, Saunders 2000, p 956. 22. Tumlin JA, Sands JM. Nephron segment specific inhibition of Na + -K + - ATPase activity by cyclosporine A. Kidney Int 1993; 43: 246. ALLOIMMUNE INDUCTION OF ENDOTHELIAL CELL-DERIVED INTERFERON-–INDUCIBLE CHEMOKINES 1 RAGHAVANPILLAI RAJU, 2 ANGELA MALLOY,TARA SHAH,RODNEY SMITH,MARTIN OAKS, AND JEFFREY D. HOSENPUD Background. The interaction between host lympho- cytes and endothelial cells on the transplanted organ is believed to play an important role in acute and chronic graft rejection. Trafficking and recruitment of lymphocytes to the site of inflammation is known to be controlled by several cytokines and chemokines. It is unclear whether endothelial cells themselves can be a source of inflammatory chemoattractant molecules on alloimmune induction. Methods. Using a semiquantitative polymerase chain reaction method, the authors analyzed the ex- pression of chemokine mRNA coding for interferon (IFN)-–induced protein 10 (IP-10) and monokine in- duced by IFN- (Mig) in a pool of human aortic endo- thelial cells. Both of these chemokines are known to be induced by IFN-. Endothelial cell-derived chemokine mRNA was assayed at rest, after IFN- activation, and after co-culture with allogeneic peripheral blood mononuclear cells (PBMC) from normal blood donors with and without a monoclonal antibody to IFN-. Fi- nally, protein release into the media was assayed us- ing an enzyme-linked immunosorbent assay to IP-10. Results. Mig and IP-10 were expressed in human endothelial cells both after IFN- treatment and after PBMC co-culture. Furthermore, the expression of both of these endothelial cell-derived chemokines was de- pendent on IFN- because PBMC-induced expression was blocked with anti–IFN-. IP-10 levels in the endo- thelial cell supernatant increased from a baseline of 13.410.8 pg/mL to 299.513.4 pg/mL (P<0.0001) with exposure to PBMC and was likewise inhibited by anti– IFN- A-b (33.817.8 pg/mL). Conclusions. Vascular endothelial cells are capable of producing inflammatory chemokines when acti- vated and potentially serve to amplify the allogeneic response. Chemoattractant molecules or chemokines are responsible for immune cell attraction and homing. There are two pri- mary classifications of currently known chemokines. One is based on specific cystine residue sequence motifs that are divided into four subfamilies, CC, CXC, C, and CX3C (1). The other, recent, classification uses physiologic features and cel- lular distribution and is divided into inflammatory and ho- meostatic chemokines (2). The interface between the cellular immune system and the allograft in most cases is the allo- graft endothelium. The interaction between alloreactive lym- phocytes with graft endothelial cells is believed to be impor- tant in eliciting or perpetuating chronic rejection of the graft. One mechanism by which this interaction could initiate or amplify an alloresponse would be to trigger the production of chemokines, which would then bring additional inflamma- tory cells to the site of the allograft (3). It has been observed that allogenic grafts differentially express various chemo- kines, and increases of chemokine receptors were also ob- served in allografts (4). Antiserum to chemokine receptor CXCR3 was found to prolong heart allograft survival, and CXCR3-deficient mice exhibited profound resistance to devel- opment of acute allograft rejection (5). In another study, the intra-allograft RNA expression of several CXC and CC che- mokines were tested during rejection of full-thickness skin grafts from B10.D2 donors on BALB/c recipients, and it was found that 3 days before rejection was manifest, CXC chemo- kines were expressed in the allograft, suggesting a possible role in recruiting primed T cells into the allograft (4). There are few data regarding the ability of endothelial cells to directly produce chemokines on interaction with allogenic lymphocytes and what stimuli elicit their production. Garcia et al. demonstrated that fractalkine, a CX3C chemokine, could be elicited in rat aortic endothelial cells by exposing them to interleukin (IL)-1, tumor necrosis factor (TNF)-, or lipopolysaccharide (LPS) (6). This was confirmed in human umbilical vein endothelial cells by Imaizumi et al. (7). Beck and colleagues investigated differential expression of CC, 1 Supported by National Institutes of Health, National Heart, Lung, and Blood Institute Grant HL56747 and St. Luke’s Research Foundation, Milwaukee, WI. Chronic Rejection Laboratory, St. Luke’s Medical Center, Milwau- kee, WI. 2 Address for correspondence: Raghavanpillai Raju, Ph.D., Neuro- muscular Autoimmunity, Building 10, Room 4N252, National Insti- tutes of Health, 10 Center Drive, Bethesda, MD 20892. Received 23 May 2002. Revision requested 9 July 2002. Accepted 11 December 2002. DOI: 10.1097/01.TP.0000058349.08707.E6 TRANSPLANTATION 1072 Vol. 75, No. 7