Biologic basis for interleukin-1 in disease

Abstract

To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in disease, investigators have studied how production of the different members of the IL-1 family is controlled, the various biologic activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family, and the complexity of intracellular signaling. Mice deficient in IL-1Beta, IL-1Beta converting enzyme, and IL-1R type I have also been studied. Humans have been injected with IL- 1 (either IL-1alpha or IL-1beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1-specific receptor antagonist (IL-1Ra) has also been tested in clinical trials. The topics discussed in this review include production and activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene expression, functions of cell-bound and soluble IL-1 receptors, the importance of the IL-1R accessory protein, newly discovered signal transduction pathways, naturally occurring cytokines limiting IL-1 production or activity, the effects of blocking cyclooxygenase and nitric oxide, and the outcomes of IL-1 and IL-1 Ra in human trials. Special attention is paid to IL-1beta converting enzyme and programmed cell death. The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth of solid tumors are also discussed. This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references. At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.

Effect of TLR agonist on infections bronchitis virus replication and cytokine expression in embryonated chicken eggs

“…IL-6. In addition, the IL-1β has also been demonstrated to be mainly involved in innate immune responses (Dinarello, 1996). In the present study, following embryonic treatment with LPS and Pam3CSK4, the IL-1β expression was increased in the CAM of ECEs.…”

The Immunophysiology of Male Reproduction

“…The archetypical pro-inflammatory cytokine, IL1 is represented by two related proteins (IL1α and IL1β) capable of binding to the same receptor to exert an almost identical range of effects. 370 These proteins are produced by many cells types, but activated monocytes and macrophage are the major source of secreted IL1. 370 Both IL1α and IL1β are single chain proteins, with only about 25% homology at the mature protein level.…”

“…370 These proteins are produced by many cells types, but activated monocytes and macrophage are the major source of secreted IL1. 370 Both IL1α and IL1β are single chain proteins, with only about 25% homology at the mature protein level. They are synthesized as 31-33 kDa precursor proteins that are cleaved enzymatically to active 17-kDa forms (Figure 19.10).…”

“…Moreover, IL1 is able to activate other signaling pathways through induction of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3)/Akt protein kinase (AKT) and tyrosine-protein kinase Src (SRC), hydrolysis of GTP, phosphatidylcholine, phosphatidylserine or phosphatidylethanolamine, release of ceramide by neutral sphingomyelinase, and release of arachidonic acid by phospholipase A 2 (PLA 2 ). 370,398 There is an IL1 type II receptor (IL1R2), which lacks a TIR domain and can act as a decoy or inhibitory receptor. 399 In cultures of Leydig cells from immature rats (10-20 days of age), IL1β caused a dose-dependent increase in DNA synthesis, and IL1α was much less potent than IL1β.…”

Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation—a perspective

“…The full details of this interaction between inflammatory signalling and FSH signalling in the Sertoli cell are unclear at present. While LPS and IL1␣ normally act via the adapter protein MyD88 and its downstream signalling pathways involving the transcription factors NFB and AP1, and the MAP kinases p38 and Jnk, these inflammatory mediators also activate several other signalling pathways, most notably the sphingomyelinase/ceramide pathway, the phospholipase A2/arachidonic acid metabolite pathway and the phosphoinositide-specific phospholipase C pathway involving diacyglycerol and inositol trisphosphate (Dinarello, 1996). Moreover, TNF␣ does not act via MyD88 at all, but activates the TRAFs via a separate mechanism entirely (Chung et al, 2002).…”