In our first review on chemokines (1), we suggested that blockade of the IL-8 receptor or inhibition of IL-8 gene expression could be a new principle for designing antiinflammatory agents. The unexpected growth of the chemokine family and consequent redundancy of the system eventually made it clear that acting at the level of chemokine gene expression was rather hopeless, but the idea of influencing inflammation with chemokine receptor antagonists has remained valid and inhibitors were recently put to the test. A new literature, including several articles in this issue of The Journal of Experimental Medicine, indicate that the idea was worth trying.
By scanning mutagenesis (2) and selective deletion or substitution of NH2-terminal residues (3, 4) it was shown that the Glu-Leu-Arg (ELR) motif preceding the first cysteine is essential for IL-8 activity. The ELR motif is conserved in...
