review · Frontiers in Immunology
This review summarises the biological properties and pathological role of Interleukin-18 (IL-18), a potent pro-inflammatory cytokine. IL-18 is crucial for host defence and regulates both innate and acquired immune responses, being produced by various cell types. Elevated levels of IL-18 are linked to several immune-related diseases, including rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease, as it can induce inflammatory and cytotoxic immune cell activities leading to autoimmunity. Existing monoclonal antibodies and drugs targeting IL-18 have shown limited effectiveness in studies. This ineffectiveness is likely due to the involvement of other cytokines and proteins in inflammatory signalling pathways. The review recommends combination drug therapies that inhibit IL-18 alongside other cytokines as a promising area for future research.
Understanding Interleukin-18's role is vital because it is a key player in both healthy immune responses and the development of autoimmune diseases. Identifying why current treatments are ineffective and proposing new strategies could lead to better therapies for chronic inflammatory conditions affecting many people.
The research highlights the need for improved therapeutic strategies for autoimmune and inflammatory diseases. While current IL-18 targeting drugs are largely ineffective, the recommendation for combination therapies suggests a pathway for developing more effective treatments. This is early-stage research, identifying a new direction for drug development that could benefit patients with conditions like rheumatoid arthritis and lupus.
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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.
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DOI: 10.3389/fimmu.2022.919973
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