Interleukin-1 (IL-1) is a potent inflammatory cytokine that was discovered in the 1970s and was first described as lymphocyte-activating factor or leukocytic pyrogen. It belongs to the IL-1 family of ligands which consists of at least 11 members. All of them play a central role in innate immune response. IL-1a and IL-1β both mediate their biologic responses via activation of the IL-1 receptor type I, whereas IL-1Ra functions as receptor antagonist.
IL-1β is the best-studied cytokine of the IL-1 family. It maintains a central function in defending the organism against infections with pathogenic microorganisms including bacteria, fungi and viruses. Also, IL-1β effects are triggered by a variety of host-derived or environmental cellular stressors such as urate crystals, asbestos and skin irritants. Apart from its physiologic role in host protection, IL-1β is known to be important in a number of severe inflammatory diseases including the rare cryopyrin-associated periodic syndromes (CAPS) and other hereditary and polygenic autoinflammatory diseases. Most of these diseases can be completely controlled by anti-IL-1β treatment. In addition, an essential function for IL-1β has been demonstrated in common diseases such as gout, type II diabetes and cancer.
Findings suggest that inflammasome-dependent IL-1β activation plays a role in different allergic disorders.
Contact hypersensitivity is characterized by T-cell driven skin inflammation elicited in response to various haptens, for example chemicals or metallic ions such as nickel. Skin irritants can induce the activation of the proinflammatory cytokine IL-1β which can then participate in Langerhans cell migration and lymphocyte recruitment, thus, promoting skin inflammation.
Asthma is characterized by chronic airway inflammation and hyperresponsiveness to external stimuli. Different experiments in mice have indicated an important role for IL-1 in Th2-related cytokine production and airway hyperresponsiveness. There is also evidence from several animal asthma models that treatment with IL-1-neutralizing drugs results in a reduced airway hyperreactivity, less inflammatory infiltration and a decrease in Th2 cytokines.
Atopic dermatitis is a Th2-mediated chronic inflammatory skin disorder in which T-cell responses to environmental or food allergens are associated with the development and aggravation of the disease. It is known that keratinocytes contain the NLRP3 inflammasome and that ultraviolet B irradiation leads to enhanced IL-1β secretion. It was shown that house dust mite allergens act as danger signals in the skin and can also induce inflammasome-dependent IL-1β secretion from keratinocytes.
The findings support a crucial role for IL-1β and inflammasome components in a variety of allergy related disorders. IL-1-neutralizing drugs have been shown to completely suppress or markedly reduce inflammatory responses in clinical studies and experimental models common allergic disorders.
Krause K, et al. The role of interleukin-1 in allergy-related disorders[J]. Current opinion in allergy and clinical immunology, 2012, 12(5): 477-484.