Abstract
Biologics that neutralize specific cytokines have improved outcomes for several immune-mediated disorders but may also increase risks for particular side effects. This article postulates potential immunologic consequences of inhibiting components of the IL-23/T-helper cell 17 pathway-the target of next-generation biologics for treating psoriasis-based on clinical phenotypes of inherent or acquired deficiencies in this pathway. Generally, downstream deficiencies (e.g., IL-17A, IL-17F) are associated with fewer disorders compared with upstream deficiencies, suggesting that selectively blocking downstream targets may result in a narrower range of side effects. However, safety of these specific inhibitions must be established in long-term studies.
MeSH terms
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Biological Products / pharmacology
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Biological Products / therapeutic use*
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Humans
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Immune System Diseases / drug therapy*
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Immune System Diseases / physiopathology
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Interleukin-17 / antagonists & inhibitors
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Interleukin-17 / deficiency*
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Interleukin-17 / genetics
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Interleukin-23 / deficiency*
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Interleukin-23 / drug effects
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Interleukin-23 / genetics
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Mutation / genetics
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Mycobacterium Infections, Nontuberculous / drug therapy
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Mycobacterium Infections, Nontuberculous / physiopathology
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Phenotype*
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Psoriasis / drug therapy
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Psoriasis / physiopathology
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Salmonella Infections / drug therapy
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Salmonella Infections / physiopathology
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Treatment Outcome
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Tuberculosis / drug therapy
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Tuberculosis / physiopathology
Substances
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Biological Products
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Interleukin-17
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Interleukin-23