Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

Abstract

Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine involved in host defense against infections and regulates the innate and acquired immune response. IL-18 is produced by both hematopoietic and non-hematopoietic cells, including monocytes, macrophages, keratinocytes and mesenchymal cell. IL-18 could potentially induce inflammatory and cytotoxic immune cell activities leading to autoimmunity. Its elevated levels have been reported in the blood of patients with some immune-related diseases, including rheumatoid arthritis, systemic lupus erythematosus, type I diabetes mellitus, atopic dermatitis, psoriasis, and inflammatory bowel disease. In the present review, we aimed to summarize the biological properties of IL-18 and its pathological role in different autoimmune diseases. We also reported some monoclonal antibodies and drugs targeting IL-18. Most of these monoclonal antibodies and drugs have only produced partial effectiveness or complete ineffectiveness in vitro, in vivo and human studies. The ineffectiveness of these drugs targeting IL-18 may be largely due to the loophole caused by the involvement of other cytokines and proteins in the signaling pathway of many inflammatory diseases besides the involvement of IL-18. Combination drug therapies, that focus on IL-18 inhibition, in addition to other cytokines, are highly recommended to be considered as an important area of research that needs to be explored.

Transcriptome analysis of bovine macrophages (BoMac) cells after infection with bovine immunodeficiency virus

“…Our studies have shown that both are significantly dysregulated following BIV infection, which consequently facilitates the establishment of the infection. In addition, this study showed that one of the inflammatory cytokines, IL-18 (18), was downregulated, which also confirms the inhibition of the inflammatory response during BIV infection (Table 4).…”

NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies

“…A 3-to-5-year follow-up study in 24 CINCA/NOMID patients treated with anakinra showed the sustained remission in most of the subjects, together with a safety profile, the improvement of physician and patients’ quality of life assessment, as well as the normalization of systemic and organ inflammation, with the exception of bone involvement which did not respond to the therapy ( 121 ). Observational studies in different cohorts of patients confirmed these results with a complete and partial remission rate ranging from 40% up to 100% among different studies ( 70 , 114 , 122 , 123 ). In conclusion, anakinra shows a good safety profile, also in pregnancy ( 124 ), and could prevent and stabilize systemic and organ-specific autoinflammatory damages, including hearing loss in DFN34 patients ( 108 , 114 ).…”

“…During the last years, IL-1b cascade inhibitors -anakinra, canakinumab, rilonacept, -the latter only approved in the US -have been shown to be effective and relatively safe, representing a breakthrough for the therapeutic management of CAPS, which are now currently treatable in both the acute phase than in the long-term maintenance (114, 115) (Table 4). Isolated reports and in vitro studies suggested anti-TNF-a agents as a valuable therapeutic option in CAPS, although they appear inferior compared to IL-1 antagonists in symptoms relief and disease control (120,121) while IL-18 inhibition, a key cytokine released upon inflammasome activation, although promising did not show positive results in preclinical and clinical studies, and currently no FDA approved IL-18 antagonist is available in the clinical practice (122). Due to the pivotal role of the NLRP3 inflammasome in a wide array of autoinflammatory and chronic inflammatory diseases, pharmacologic research of NLRP3 cascade inhibitors is actively growing and many compounds targeting NLRP3 inflammasome and its related pathway are currently investigated, as extensively reviewed by Zahid et al (123).…”

Biomarkers of atopic dermatitis: a meta-analysis over the last decade

“…IL-18, a member of the IL-1 family, can induce IFN-γ to exert proin ammatory effects [14,15]. In AD, the function of IL-18 depends on its surrounding cytokine environment.…”