ILAR Journal Online, Volume 40(4) 1999: Animal Models of Inflammation

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ILAR Journal V40(4) 1999
Animal Models of Inflammation

Introduction
Peter A. Ward

Chemokines are chemotactic cytokines that are represented by the interleukin (IL¹)-8 family of interleukins and exist as four different families based on the structures and positions of cysteine residues. At least 40 different chemokines are currently known. The developing application of microarray displays for large-scale enumeration of mRNA expression in tissues will provide another dimension of complexity in trying to understand what the chemokines are doing in biological responses. This situation, together with the findings that chemokine receptors are "promiscuous" (multiple chemokines interact with the same and with other receptors), indicates the daunting challenges in understanding the biological functions of these molecules. The other large problem is the extent to which there is functional redundancy in chemokines, making it difficult to define their biology in experimental systems in which individual chemokines are blocked (by antibody) or absent due to induced mutations that preclude expression of an individual chemokine.

The papers in this issue of ILAR Journal underscore the enormous complexity of chemokines in biological responses, whether, for example, as inflammatory responses to bacterial infections, to allergic triggers, to immune-relaed products such as immune complexes, to tumor cells, or to other angiogenic inducers. Responses involving chemokine expression almost invariably involve activation of nuclear factor kappa B (NFkB¹), which is required for gene activation but is tightly regulated by inhibitory factor kappa B (IkB¹), whereas mediators such as IL-1 and tumor necrosis factor alpha (TNFa¹) activate NFkB, setting off a proinflammatory cascade. Interleukins such as IL-10 and IL-13 have opposite effects, preventing this gene activation. Not surprisingly, it is also evident that chemokine expression is facilitated by two products of activated macrophages, TNFa and C5a. The expression of these two factors leads to autocrine stimulation of chemokine expression in macrophages both in vitro and in vivo. The "networking" of mediators is a common theme of the inflammatory response.

This issue of ILAR Journal underscores the vitatlity of the chemokine field. We almost surely will be in for surprises in the coming years.

¹ Abbreviations used in this introduction: IkB, inhibitory factor kappa B; IL, interleukin; NFkB, nuclear factor kappa B; TNFa, tumor necrosis factor alpha.