Recent developments in modulating chemokine networks

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Abstract
Chemokines are a family of small cytokines involved in the recruitment and activation of a large variety of cell types. They were originally identified because of their role in recruiting cells during inflammation, but have since been shown to be involved in such diverse activities as the orchestration of the immune response in routine immuno-surveillance, embryonic development and angiogenesis. Early studies showed that different leukocyte populations expressed different chemokine receptors, implying that chemokine receptor antagonists could potentially be highly selective anti-inflammatory molecules. The pharmaceutical interest in an antichemokine receptor strategy expanded with the discovery that two chemokine receptors are also critical for the pathway by which HIV invades host cells. In this review, we discuss the recent progress made in identifying potential therapeutics that can modulate chemokine networks, starting with antibodies, modified chemokines and chemokine binding proteins. Over the last two years the patent literature on non-peptidic small molecule antagonists has started to mature. We review the state of the art, and speculate on the future directions of this exciting field.