From basic science to clinical practice: use of cytokines and chemokines as therapeutic targets in renal diseases

Cytokines are soluble factors that are critical for the pathophysiology of the immune system and exhibit other important functions. Recently, several cytokines have been suggested as possible therapeutic targets in renal diseases, and their possible clinical utility is now being tested in phase I-II clinical trials. Chemokines are a family of small, structurally related, cytokines that regulate cell trafficking of different subsets of leukocytes, thus critically regulating renal inflammation. The initial hope that targeting of chemokines may result in the attenuation of inflammation without inducing generalized immunosuppression is hampered by the redundancy in chemokine activity with the potential risk of severe side effects. However, a deep comprehension of the complex biology of chemokines has allowed the identification of some chemokine receptors as possible theraputic targets in the pathogenesis of selected renal diseases, in as much as they display non-redundant roles. More importantly the discovery of the critical involvement of CXCR3 in transplant tolerance, suggests that this chemokine receptor might represent a critical target for treatment of both acute rejection and chronic allograft nephropathy. Finally, we recently demonstrated that pretransplant serum levels of CXCL10/IP-10, a CXCR3-ligand, represent a clinically useful parameter for the identification of subjects exhibiting high risk of acute rejection, chronic allograft nephropathy and graft failure, a finding that might be used to individualize immunosuppressive therapies.