INTERLEUKIN-8 IS A CYCLOSPORINE-A BINDING-PROTEIN

Inflammatory immune reactions occur during transplant rejections and a utoimmune diseases. Such reactions are mediated by cytokines, includin g interleukin-8 (IL-8). Cyclosporin A (CsA) exerts immunosuppressive a ctivities1,2 by binding to immunoregulatory proteins termed cyclophili ns3. The anti-inflammatory effects of CsA are still not fully understo od. Searching for novel neutrophil-activating proteins, we observed th at an antiserum against human recombinant Interleukin-8 (IL-8) cross-r eacted with cyclophilins in Western blots. Furthermore, native IL-8 wa s found to specifically bind CsA, whereas biologically inactive analog s of CsA were not bound by IL-8. Putative binding sites for CsA on IL- 8 could be identified on the basis of structural similarities between IL-8 and cyclophilin. However, IL-8 lacks peptidyl-prolyl-isomerase (P Plase) enzyme activity, which is regarded as a characteristic of cyclo philins4,5,6. We conclude that the specific binding of CsA to IL-8 may explain some of the anti-inflammatory effects of CsA. IL-8 may be a n ovel member of the cyclophilins lacking PPlase activity.