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AT-A-GLANCE

AT-A-GLANCE

  • Immunobiologics are drugs defined as antibodies and proteins engineered from living organisms that induce or alter immune responses by interacting with specific biologic targets.

  • Those used to treat cutaneous disease and cancer include recombinant cytokines and growth factors, monoclonal antibodies, and fusion proteins.

  • Targeting the immune system with biologics may result in an increased risk of infections and malignancies.

Immunobiologics are compounds synthesized in living organisms that exhibit immune modulatory properties for therapeutic purposes. They consist of recombinant cytokines, growth factors, antibody-based agents, and fusion proteins. Many cytokines are known to play critical roles in the most common of dermatologic conditions, including psoriasis and atopic dermatitis, and, as of this writing, more than 10 immunobiologic agents, mostly humanized monoclonal antibodies, have been approved or will soon be approved for these conditions since the last version of this chapter. Herein, we briefly discuss cytokines as it is difficult to discuss immunobiologics that target specific cytokines without understanding the fundamental role of the cytokine in biologic or immunologic processes. Besides tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-1, some of the first cytokines to be recognized as central to immunopathogenesis of common skin diseases, cytokines such as IL-18, IL-22, and IL-23, are now seen to play critical roles in Still disease (IL-18), epidermal psoriatic hyperproliferation (IL-22), and T-helper cell type 17 (Th17) maintenance (IL-23). We emphasize the newer cytokines and treatments that are in development and refer to excellent reviews to highlight the clinical usefulness of older agents. Lastly, we point out some of the unique side effects that are sometimes observed with the new biologic agents as these (often rare) side effects take time to recognize and to characterize in the literature. When possible, we depict the cellular events that mediate cutaneous inflammation and identify the molecular interactions affected by specific immunobiologic agents in relevant figures.

INTERLEUKIN 1

IL-1 was the first cytokine to be detected in skin1 and is now regarded as the prototypical member of a family of 11 structurally related cytokines (Fig. 193-1). IL-1 is a fundamental cytokine for directing epidermal responses to injury and infection. Although pro-IL-1α is active as a cell membrane–associated cytokine, under conditions of cell stress, cytoplasmic pro-IL-1α also can be rapidly processed and secreted.2,3 In contrast, pro-IL-1β is inactive and always requires the action of a protease for activity. A diverse array of stimuli, including cell stress, infection, and local danger signals, trigger the assembly of macromolecular inflammasome complexes that activate caspase-1, which then cleaves pro-IL-1β to its active form.4 Once activated, both IL-1α and IL-1β can bind IL-1 receptor 1 (R1) on the surface on target cells, driving signal transduction (Fig. 193-2). A decoy receptor, IL-1R2, that has a shorter cytoplasmic tail devoid of signaling domains and unable to initiate signal transduction, can be expressed on the cell surface. IL-1 signaling is also controlled ...

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