Published by Beata Boczkowska, Ph.D. on
IL-18 is a potent pro-inflammatory cytokine that plays a vital role in the body's defense against infections and regulates both the innate and acquired immune response. Understanding the balance between IL-18 and its binding protein, IL-18BP, is crucial as their dysregulation can lead to adverse outcomes.
Naturally IL-18 exists in two forms- pro IL-18 and the mature IL-18. It is first present in the pro-form precursor and lacks the signal sequence required for secretion. ICE (IL-1β Converting Enzyme) or Caspase 1 cleaves Pro-IL-18 activating IL-18. This active form is seen in body tissues and carries out IL-18 function which is essential in immune defenses. Whereas the IL-18 binding protein is a naturally secreted molecule that binds to and neutralizes IL-18, inhibiting the interaction between IL-18 and IL-18R, thereby reducing IFN γ induction. Hence, the dysregulation of the IL-18/IL-18BP balance has various biological effects and can lead to pathological outcomes. Both IL-18 and IL18BP have been associated with the development of psoriasis, atopic dermatitis (AD), lupus erythematosus (LE), and other inflammatory skin diseases. For certain types of cancers, such as pancreatic cancer and multiple myeloma, IL-18 has the potential to have pro-tumoral activity. While IL-18 can enhance host immune responses, caution should be exercised when considering IL-18 therapy due to its potential to also promote cancer aggressiveness.
Given the biological properties of IL-18 and its significant role in various diseases, it is no wonder that extensive attention is being directed towards IL-18 in drug discovery and therapy research. Overall, the therapeutic effects of IL-18 therapy involve stimulating monocytes, NK cells, and T cells, leading to the production of IFN-γ and other cytokines within the body. IL-18 seems to primarily function as a costimulatory cytokine, suggesting that its optimal utilization in cancer immunotherapy could involve combining it with other immunostimulatory cytokines, vaccines, or monoclonal antibodies. Currently, drug therapy is more focused on IL-18 inhibitors or agonists in addition to other cytokines. The inhibitors and IL-18BP drugs in clinical trials and preclinical studies for the treatment of inflammatory diseases.
