Hamdan Medical Journal (previously the Journal of Medical Sciences)

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Interleukin-1: the paradigm for multifunctional inflammatory cytokines

Charles A Dinarello
Published in : Journal of Medical Sciences ; Vol 1, No 1 (2008)
DOI : 10.2174/1996327000801010008

Abstract


Cytokines affect nearly all organ systems whether Cytokines affect nearly all organ systems whether in health or disease. In disease or any challenge to the survival of the host, the sub-class of cytokines, classified as “pro-inflammatory cytokines” evokes rapid and profound inflammatory responses. Interleukin-1 (IL-1) was first studied for its ability to cause fever and acute phase changes in response to infection and in many ways established the paradigm for the redundancy of similar inflammatory cytokines that were to be discovered in subsequent years. The paradigm change was based on the ability of IL-1 to induce multiple biological effects and as a result, established the concept that a single molecule evoked a myriad of seemingly unrelated changes in responding cells and in animals. In general, the explanation for the multiple activities lies in the ubiquitous presence of the IL-1 receptor on nearly all cells. Another explanation for these multiple activities is the induction of a set of genes, which are not expressed in health but rather in disease. For example, the induction of prostaglandins via the inducible cyclooxygenase-2, the death of the insulin-producing beta cells in the islets of Langerhans due to the inducible nitric oxide and the release of neutrophils from the bone marrow via the induction of granulocyte colony stimulating factor. Each activity was initially viewed as seemingly unrelated, although clearly IL-1-inducible events. Today, following the identification of IL-1 receptors and post-receptor IL-1 signaling kinases, these events are far less unrelated. Nevertheless, since the initial studies on IL-1, the multiple effects of pro-inflammatory cytokines are readily accepted as part of biology. The biology of IL-1 took a major leap when humans were injected with IL- 1 and multiple systemic effects were observed as well as a set of symptoms unknown from animal studies. In addition, the potency of the cytokine for humans was established to be in the low picomolar range.

 


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