Abstract
Localized tissue disruption quickly elicits systemic alterations in the biochemical, physiologic, and immunologic status of the host (1–3). The hypothesis that a circulating mediator(s) produced by injured tissues orchestrates the “acute phase” alterations in the “chemistry of the host” (1–4) has now been extensively validated (5, 6). It has become amply clear in the last 3 years that the cytokine interleukin 6 (IL-6) plays a pivotal role in mediating the host response to tissue injury. Elevated levels of IL-6 are readily detected in body fluids during the course of microbial infections, autoimmune diseases, and neoplasia (6). It is the purpose of this review to highlight some recent advances in experimental IL-6 research and to discuss new clinical insights on the role of IL-6 in the pathophysiology of infection and cancer. The thesis that IL-6, in addition to mediating the systemic host response to neoplastic disease, may itself promote the proliferation of neoplastic cell elements adds a novel dimension to this discussion.
Clinical observations that we would today ascribe in large part to the effects of IL-6 were recorded at least 2500 years ago. The central tenet of Hippocratic medicine (approximately 400 B.C.) was based on the empirical observation that blood withdrawn from an acutely ill person, when allowed to stand, separated into four distinct layers or “humors” as it clotted (melancholia, sanguis, phlegm, and cholera) (7). The scientific basis for the appearance of a phlegm or crusta inflammatoria (the fibrin clot or “buffy coat”) in blood from diseased individuals was elucidated in 1921 and is the enhanced sedimentation of erythrocytes (7–9). It is understood today that the enhancement of the erythrocyte sedimentation rate during acute infections largely reflects a change in plasma protein composition (particularly an increase in the fibrinogen level) that is collectively referred to as the “acute phase” plasma protein response (5, 6, 9, 10).
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