Interleukin‐1 as a Common Denominator from Autoinflammatory to Autoimmune Disorders: Premises, Perils, and Perspectives

Abstract

A complex web of dynamic relationships between innate and adaptive immunity is now evident for many autoinflammatory and autoimmune disorders, the first deriving from abnormal activation of innate immune system without any conventional danger triggers and the latter from self-/non-self-discrimination loss of tolerance, and systemic inflammation. Due to clinical and pathophysiologic similarities giving a crucial role to the multifunctional cytokine interleukin-1, the concept of autoinflammation has been expanded to include nonhereditary collagen-like diseases, idiopathic inflammatory diseases, and metabolic diseases. As more patients are reported to have clinical features of autoinflammation and autoimmunity, the boundary between these two pathologic ends is becoming blurred. An overview of monogenic autoinflammatory disorders, PFAPA syndrome, rheumatoid arthritis, type 2 diabetes mellitus, uveitis, pericarditis, Behçet's disease, gout, Sjögren's syndrome, interstitial lung diseases, and Still's disease is presented to highlight the fundamental points that interleukin-1 displays in the cryptic interplay between innate and adaptive immune systems.

PCR array and protein array studies demonstrate that IL-1β(interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes

“…Adipocytes both exhibit immune cell functions and prime inflammation in a manner that it is independent of macrophages. Macrophages themselves not only participate directly in the inflammatory response in adipose tissue being recruited as tissue mass expands in obesity (Weisberg et al, 2003;Xu et al, 2003), but they also stimulate the production of inflammation- stimulates the production of inflammation-related factors by adipocytes is essentially unknown, despite the central role of this cytokine in inflammation and disease processes in other tissues (Fietta et al, 2014;Lopalco et al, 2015). Nevertheless, IL-1β has been shown to be a regulator of IL-6 production by human preadipocytes (O'Hara et al, 2012), and to stimulate the expression and release of IL-6 and MCP-1 in human fat cells (Gao et al, 2014).…”

“…The proinflammatory cytokine TNFα has a substantial stimulatory effect, increasing the expression and release of other inflammation-related factors including IL-6, NGF (nerve growth factor), MCP-1 (monocyte chemoattractant protein-1), MMP1 and MMP3 (matrix metalloproteinases 1 and 3) (Wang et al, 2005;O'Hara et al, 2009). There has, however, been little focus on the extent to which another classical pro-inflammatory cytokine, IL-1β (interleukin-1β) -which is implicated in a wide range of inflammatory diseases in other cells and tissues (see (Fietta et al, 2014;Lopalco et al, 2015)) -is important in stimulating the inflammatory response in adipocytes.…”

The inflammasome as a target for pain therapy

“…The principal species, IL-1b, possesses strong pro-inflammatory effects on a variety of cells, and its aberrant production contributes to acute and chronic inflammation and pain. 1 2 Notably, increased IL-1 activity is associated with autoimmune disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease, multiple sclerosis (MS), and Alzheimer's disease (AD), [1][2][3][4] which are all conditions in which pain is a common complaint. The pain-inducing mechanisms of IL-1b include the direct activation of neuronal activity in the peripheral and central nervous system, and IL-1b acts as a mediator that stimulates the production of additional algogenic substances.…”

Role of Interleukin 1 in the Development of Human Diseases

“…Гиперпродукция ИЛ1β характерна для так называе-мых наследственных аутовоспалительных заболеваний [5,25], многие из которых развиваются в раннем детском воз-расте и характеризуются рецидивирующими атаками сис-темного воспалительного процесса, проявляющегося по-ражением суставов, кожи, гиперпродукцией острофазовых белков сыворотки. Именно эти заболевания являются од-ними из первых и нередко единственными официальными показаниями для применения ГИБП, подавляющих актив-ность ИЛ1.…”

“…Предполагается, что гиперпродукция «провоспали-тельного» цитокина -ИЛ1 -во многом определяет «пере-крест» между аутоиммунитетом и аутовоспалением, харак-терный для многих ИВЗ [3][4][5].…”