Mechanisms of interieukin-1β release

Interleukin-1 beta (IL-1 beta) is a potent proinflammatory cytokine that initiates and amplifies a wide variety of effects associated with innate immunity and host responses to microbial invasion and tissue injury. Production and release of IL-1 beta are stimulated by either pathogen-associated molecular pattern molecules (PAMPs) or damage-associated molecular pattern molecules (DAMPs) and involve several steps. IL-1 beta is first synthesized as biologically inactive pro-IL-1 beta, then processed into mature, biologically active IL-1 beta by caspase-1, and subsequently released into the extracellular milieu. Whereas a large body of recent publications has greatly increased our knowledge of the mechanisms involved in production and processing of IL-1 beta, we are only beginning to understand mechanisms of IL-1 beta P secretion. This review highlights the different models of a non-classical secretory pathway used by monocytes, macrophages and dendritic cells to export the leaderless cytokine IL-1 beta. In particular, five different release mechanisms have been suggested, namely (i) exocytosis of IL-1 beta-containing secretory lysosomes, (ii) release of IL-1 beta from shed plasma membrane microvesicles, (iii) fusion of multivesicular bodies with the plasma membrane and subsequent release of IL-1 beta-containing exosomes, (iv) export of IL-1 beta through the plasma membrane using specific membrane transporters, and (v) release of IL-1 beta upon cell lysis. Reasons for the diversity of IL-1 beta secretory pathways remain to be elucidated. A better understanding of IL-1 beta release mechanisms is of great therapeutic relevance and may help in the development of strategies aimed at reducing the severity of inflammatory and autoimmune diseases. (C) 2008 Elsevier GmbH. All rights reserved.