Abstract
Cytokines are the most important soluble mediators of inflammation. Rare pediatric diseases provided exemplar conditions to study the anti-inflammatory efficacy of new generation therapies (biologics/biopharmaceuticals) selectively targeting single cytokines. Monoclonal antibodies and recombinant proteins have revolutionized anti-inflammatory therapies in the last two decades, allowing the specific targeting of single cytokines. They are very effective in extinguishing inflammation from outside the cell, even with the risk of an excessive and prolonged immunosuppression. Small molecules can enter the cell and shutdown the valve of inflammation by directly targeting signal proteins involved in cytokine release or in response to cytokines. They are orally-administrable drugs whose dosage can be easily adjusted to obtain the desired anti-inflammatory effect. This could make these drugs more suitable for a wide range of diseases as stroke, gout, or neurological impairment, where inflammatory activation plays a pivotal role as trigger. Autoinflammatory diseases, which have previously put anti-cytokine proteins in the limelight, can again provide a valuable model to measure the real potential of small inhibitors as anti-inflammatory agents.
Highlights
Cytokines are soluble mediators involved in signaling between different cells
An autoinflammatory diseases associated with excessive release of IL-1β, due to constitutive activation of the NLRP3 inflammasome platform; Mevalonate Kinase Deficiency, in which increased release of IL-1β is the indirect result of a metabolic defect involving the biosynthesis of sterols; and interferonopathies, which are monogenic disorders similar to Systemic Lupus
Cryopyrin-associated periodic syndromes (CAPS) are a group of rare, monogenic autoinflammatory diseases arising from mutations in the Cryopyrin gene
Summary
Cytokines are soluble mediators involved in signaling between different cells. They are important in the immune system, but several cytokines can be produced by non-immune cells and can act on non-immune tissues, such as bone, muscle, and endothelia [1,2]. The same disorders can provide the ideal setting to study the action and the potential of novel molecules targeting cytokine signaling. An autoinflammatory diseases associated with excessive release of IL-1β, due to constitutive activation of the NLRP3 inflammasome platform; Mevalonate Kinase Deficiency, in which increased release of IL-1β is the indirect result of a metabolic defect involving the biosynthesis of sterols; and interferonopathies, which are monogenic disorders similar to Systemic Lupus. We here discuss the potential and the theoretical limits of novel therapeutic strategies based on small molecules
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
