====== Interleukin 18 ======


[[Interleukin]]-18 (IL18, also known as [[interferon gamma]] inducing factor) is a protein which in humans is encoded by the IL18 gene.

The protein encoded by this gene is a proinflammatory cytokine.


IL-18 is a cytokine that belongs to the IL-1 superfamily and is produced by macrophages and other cells. IL-18 works by binding to the interleukin-18 receptor, and together with IL-12 it induces cell-mediated immunity following infection with microbial products like lipopolysaccharide (LPS). After stimulation with IL-18, natural killer (NK) cells and certain T cells release another important cytokine called interferon-γ (IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells.

The combination of this cytokine and IL12 has been shown to inhibit IL-4 dependent IgE and IgG1 production, and enhance IgG2a production in B cells. IL-18 binding protein (IL18BP) can specifically interact with this cytokine, and thus negatively regulate its biological activity.

===== Clinical significance =====

Apart from its physiological role, IL-18 is also able to induce severe inflammatory reactions, which suggests its role in certain inflammatory disorders.

Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein to interleukin 18 are significantly increased in adenomyosis patients in comparison to normal people, indicating a role in its pathogenesis.

IL-18 has been implicated as an inflammatory mediator of Hashimoto's thyroiditis, the most common cause of autoimmune hypothyroidism. IL-18 is up regulated by interferon-gamma.

IL-18 has also been found to increase the Alzheimer's disease-associated amyloid-beta production in human neuron cells.
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Rashad et al., from  [[Sendai]], [[Japan]] showed the intense activation of [[immune cell]]s, particularly the [[microglia]], along with the increase in [[macrophage]] activity and [[NLRP3]] [[inflammasome]] activation that is indicated by NLRP3, [[Interleukin 1 beta]] (IL-1β), and [[Interleukin 18]] gene and [[caspase 1]] [[upregulation]] and [[cleavage]] as well as [[pyroptosis]].

[[Leukocyte]]s were observed in the brain [[parenchyma]], indicating a role in [[cerebral venous thrombosis]] (CVT)-induced [[inflammation]]. In addition, [[astrocyte]]s were activated, and they induced [[glial scar]] leading to parenchymal contraction during the [[subacute]] stage and [[tissue]] loss. [[MMP9]] was responsible primarily for the [[BBB]] breakdown after CVT and it is mainly produced by [[pericyte]]s. MMP9 activation was observed before inflammatory changes, indicating that BBB breakdown is the initial driver of the pathology of CVT. These results show an inflammation driven pathophysiology of CVT that follows MMP9-mediated BBB breakdown, and identified several targets that can be targeted by pharmaceutical agents to improve the [[neuroinflammation]] that follows CVT, such as MMP9, NLRP3, and IL-1β. Some of these pharmaceutical agents are already in clinical practice or under clinical trials indicating a good potential for translating this work into patient care
((Rashad S, Niizuma K, Sato-Maeda M, Fujimura M, Mansour A, Endo H, Ikawa S,
Tominaga T. Early BBB breakdown and subacute inflammasome activation and
pyroptosis as a result of cerebral venous thrombosis. Brain Res. 2018 Jul 4. pii:
S0006-8993(18)30362-7. doi: 10.1016/j.brainres.2018.06.029. [Epub ahead of print]
PubMed PMID: 29981290.
)).