Interleukin-23 Involved in Fibrotic Autoimmune Diseases: New Discoveries

Abstract

Interleukin (IL)-23 is a central pro-inflammatory cytokine with a broad range of effects on immune responses. IL-23 is pathologically linked to the induction of the production of the pro-inflammatory cytokines IL-17 and IL-22, which stimulate the differentiation and proliferation of T helper type 17 (Th17) cells. Recent discoveries suggest a potential pro-fibrotic role for IL-23 in the development of chronic inflammatory autoimmune diseases characterized by intense fibrosis. In this review, we summarized the biological features of IL-23 and gathered recent research on the role of IL-23 in fibrotic autoimmune conditions, which could provide a theoretical basis for clinical targeting and drug development.

Changes in Serum IL-12 Levels following the Administration of H1-Antihistamines in Patients with Chronic Spontaneous Urticaria

“…The bimodal effects of IL-12-derived cytokines are in line with the idea that IL-12, on the one hand, is a crucial factor driving Th1 responses and IFN-y production in the initial stages of an immune response, and on the other hand, IL-12 may play a later immunoregulatory role in advanced-stage inflammation [64]. Proinflammatory cytokines facilitate the initiation and propagation of autoimmune inflammation and stimulate immune cells, while anti-inflammatory cytokines inhibit inflammation and suppress the immune system [3].…”

“…IL12A is constitutively expressed in various cells, while IL12B is expressed only in IL-12p70-producing cells [ 31 ]. The production of bioactive IL-12p70 requires the simultaneous expression of both subunits in the same cell, and the heterodimer secretion is limited by the availability of IL12p35 [ 60 , 61 , 62 , 63 , 64 ].…”

“…Recent independent studies have validated the concept that IL-12p35 and IL-12p40 are stable cytokines with independent functions, active as monomers, homodimers, and heterodimers, which can have antagonistic, additive, or synergistic influences on the same biological process [ 43 , 44 ]. IL-12-derived cytokines promote a particular phenotype—for example, Th1 (bioactive IL-12), Th2/anti-inflammatory (antagonistic IL-12(p40)2 homodimers)—in a pathogenic microenvironment [ 61 , 62 , 63 , 64 ].…”

“…Proinflammatory cytokines facilitate the initiation and propagation of autoimmune inflammation and stimulate immune cells, while anti-inflammatory cytokines inhibit inflammation and suppress the immune system [ 3 ]. Consequently, a dynamic and ever-changing balance between IL-12p35, IL-12p40, and IL-12p70, with pro- and anti-inflammatory properties, could potentially play a role in the pathogenesis and clinical characteristics of CSU, initiating/regressing inflammation, recovering from acute phases of the disease, and monitoring the anti-H1 response in CSU patients [ 5 , 43 , 44 , 59 , 62 , 63 , 64 ].…”