Chemokines as molecular targets for therapeutic intervention.

Despite the youth of the chemokine field, many antagonists of chemokine function have already been identified and tested at the preclinical level. These include neutralizing antibodies, peptidyl and non-peptidyl antagonists and non-specific immunosuppressive agents. These early studies suggest that chemokine agonists have the potential to regulate many diseases, ranging from HIV-1 infection and tumor growth to acute and chronic inflammation. Clinical application will depend on pharmaceutical development. Great strides have been made in defining structural domains of the chemokines involved in receptor binding and activation. The identification of receptors is rapidly progressing, but with 50 potential ligands and 15 characterized receptors, it is obvious that additional molecular studies are needed. The intriguing observation that several pathogens either use chemokine receptors as entry portals or produce chemokine decoys to subvert the immune system suggests that there is much to be learned about the immune system from studies of "virokines." Future studies should lead to the discovery and design of more effective inhibitors and antagonists with therapeutic benefit.