# Downstream Cytokine Changes Post-Risankizumab

What downstream cytokine changes occur after risankizumab-mediated IL-23 inhibition?

I'll search for studies on cytokine pathway changes downstream of IL-23 blockade by risankizumab.

## Findings from Analysis

The downstream cytokine picture from risankizumab's IL-23p19 blockade is well-characterized across multiple biomarker studies, and the changes are consistent enough to sketch with reasonable confidence.

### Key Cytokine Changes

1. **IL-17 isoforms (IL-17A, IL-17C, IL-17F)**  
   - Most robustly reduced downstream targets.  
   - The KEEPsAKE 2 biomarker substudy found significant decreases in IL-17A and IL-17C by week 4, continuing to decline through week 24. Ravishankar et al. 2023  
   - A Crohn's disease phase 2b analysis showed significant reductions in plasma IL-17 and colonic IL-17A RNA. Salas et al. 2019  
   - A 2019 JACI skin biopsy study extended this to demonstrate downregulated IL-17 pathway transcriptomics within 4 weeks. Visvanathan et al. 2019

2. **IL-22**  
   - Consistently reduced in plasma and tissue.  
   - Crohn's phase 2b data showed significant decreases in circulating IL-22 protein by week 12. Salas et al. 2019  
   - A study found declines in CD8+IL-22+ T cells, but baseline IL-22 levels or reduction magnitude did not predict clinical response. Salas et al. 2019

3. **IL-1β**  
   - Drops consistently across both psoriasis and Crohn's disease data.  
   - Significant declines in plasma IL-1β and colonic IL-1β RNA were confirmed by multiple studies. Salas et al. 2019; Diotallevi et al. 2025

4. **IL-6**  
   - Decreases correlated with improvements in musculoskeletal disease activity (PASDAS) and skin outcomes (PASI). Ravishankar et al. 2023

5. **Th17 cell subset dynamics**  
   - IL-23 inhibition selectively downregulates certain IL-23 receptor-expressing T17 subsets, while increasing others. Kim et al. 2025

6. **Treg induction**  
   - Treg frequency increased within 16 weeks of risankizumab treatment, negatively correlating with baseline PASI.

7. **Macrophage Polarization**  
   - Promotion of M2-type (anti-inflammatory) macrophages at the expense of M1-type, confirmed by in vitro ELISA. Yuan et al. 2025

### Overall Pattern
Across indications, the core pattern is a hub-and-spoke collapse: primary blockade of IL-23 → reduced Th17, Tc17, ILC3, γδ T cell activation → downstream suppression of IL-17A/C/F, IL-22, IL-1β, IL-6, IL-8, CCL20, and CXCL1. This evidence emerges early (by week 4 at the latest), and further studies could surface additional data on related cytokines.