On the other hand, contrary to IL-17 inhibition, IL-23p19 blockade does not increase the risk of candida infection, nor is it associated with inflammatory bowel disease worsening.
After 1 year of follow-up, the odds of having IBD were 2.85 (<i>p</i> = .0213) and 1.42 (<i>p</i> = .1891) times higher in the anti-IL-17a and PDE4i cohorts, respectively, compared to the biologic-naïve cohort, and 2.86 (<i>p</i> = .0253) and 1.21 (<i>p</i> = .4978) times higher compared to the non-IBD-indicated biologic cohort.
Reduction of CD68+ macrophages and decreased IL-17 expression in intestinal mucosa of patients with inflammatory bowel disease strongly correlate with endoscopic response and mucosal healing following infliximab therapy.
On the other hand, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering or worsening of inflammatory bowel disease.
Upregulation of Bcl-2 and IL-17 by HSPA4 would control apoptosis of inflammatory cells and immune response in the gut, which might develop treatment resistance in IBD.
However, given the complexity and probably the redundancy of pathways leading to IBD lesions, and the fact that Th17 cells may also have protective functions, neutralization of IL-17Afailed to induce any improvement in CD.
IL-23-mediated Th-17 cell activation and stimulation of IL-17-driven pro-inflammatory axis has been associated with autoimmunity disorders such as Inflammatory Bowel Disease (IBD) or Crohn’s Disease (CD).
IL-17A and the transcription factor retinoic acid receptor-related orphan receptor γt (RORγt) play fundamental roles in the pathogenesis of inflammatory bowel diseases; in human studies, we detected a dense infiltration of RORγt-dependent CD4(+) IL17A(+) T helper (Th)17 cells in specimens of CRC, ulcerative colitis, and ulcerative colitis-associated colorectal cancer.
An efficient strategy for IBD therapy is represented by the combination of IL-17A and IL-17F in acute IL-17A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17F knockout, DSS-induced colitis have been observed.
TAK-828F strongly inhibited IL-17 gene expression with IC<sub>50</sub> values from 21.4 to 34.4 nmol/L in PBMCs from anti-TNF mAb naive and treatment-failure patients of IBD.
The function of these lymphocyte subpopulations in the development of IBD is well-known, since they produce a number of pro-inflammatory cytokines, such as interferon-γ and interleukin-17A, which in turn activate mucosal proteases, thus leading to the development of intestinal lesions, i.e., ulcers, fistulas, abscesses, and strictures.
IL-17-producing Th17 cells and IFN-γ and IL-17 double-producing Th1/17 cells have been identified as the pathogenic cells in inflammatory bowel disease (IBD).
Serious adverse effects occur less frequently and specific to the psoriasis treatment option, such as inflammatory bowel disease and candida infections with IL-17 inhibitors, tuberculosis with certolizumab pegol, and psychiatric events with apremilast.