Interleukin 18

Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a is_associated_with::protein which in humans is encoded by the IL18 is_associated_with::gene. The protein encoded by this gene is a is_associated_with::proinflammatory cytokine.

Function
IL-18 is a is_associated_with::cytokine that belongs to the IL-1 superfamily and is produced by is_associated_with::macrophages and other cells. IL-18 works by binding to the is_associated_with::interleukin-18 receptor, and together with IL-12 it induces is_associated_with::cell-mediated immunity following infection with microbial products like is_associated_with::lipopolysaccharide (LPS). After stimulation with IL-18, natural killer (NK) cells and certain is_associated_with::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 is_associated_with::B cells. IL-18 binding protein (is_associated_with::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 is_associated_with::IL-18 receptor mRNA and the ratio of IL-18 binding protein to interleukin 18 are significantly increased in is_associated_with::adenomyosis patients in comparison to normal people, indicating a role in its pathogenesis.

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

IL-18 has also been found to increase the is_associated_with::Alzheimer's disease-associated is_associated_with::amyloid-beta production in human neuron cells.

Age-related macular degeneration (AMD)
IL-18 acts as a guardian of eyesight by eliminating is_associated_with::VEGF from the eye, thereby suppressing the production of damaging blood vessels behind the is_associated_with::retina at the back of the eye. In pre-clinical models, IL-18 was administered intravenously, improving on the regular ocular injections of VEGF antibodies that is the is_associated_with::standard of care. AMD is one of the most common forms of blindness among the aging. The two forms of AMD are 'dry' (the majority of cases) and wet, which causes 90% of blindings. Wet AMD causes sub-retinal blood vessels to grow excessively, which causes almost immediate central blindness. Prior treatment options for wet AMD were limited to the condition's end stages.