The dual role of interleukin-22: balancing protection and risk in pregnancy during inflammatory challenges

To investigate the potential of recombinant interleukin-22 (rIL-22) in preventing inflammation-triggered abortion.

Experimental animal study using wild type (WT, C57BL/6J) and IL-22 knockout (IL-22⁻/⁻) mice aged 7-14 weeks. Abortion was induced via intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 8.5.

Pregnant WT and IL-22⁻/⁻ mice (n = 6/group for tissue collection at gestational day 8.5+48 hours; n = 3/group for monitoring to delivery at gestational day 20.5).

Tail vein injection of recombinant IL-22 at varying doses (5, 10, or 20 µg/mouse) prior to LPS administration.

Pregnancy outcomes (abortion vs. live delivery), endometrial mucosal architecture, epithelial barrier integrity (transepithelial electric resistance), gene expression profiles (qRT-PCR), protein distribution (IHC/IF), and immune marker levels in amniotic fluid (multiplex immunoassay).

Administration of rIL-22 to IL-22⁻/⁻ mice restored endometrial mucosal architecture to levels similar to WT animals and prevented abortion in a dose-dependent manner. rIL-22 treatment rescued pregnancy in IL-22⁻/⁻ mice at 5-20 µg/mouse, whereas only ≤10 µg/mouse was effective in WT mice. High-dose rIL-22 (20 µg/mouse), when combined with LPS, negatively affected pregnancy outcomes in WT mice, and 20 µg alone resulted in adverse outcomes in both genotypes.

Interleukin-22 emerges as a promising therapeutic target in reproductive medicine, offering potential avenues for preserving pregnancy in the face of inflammatory challenges. However, increased levels of IL-22 could be associated with reproductive failures, emphasizing the delicate balance required for immune regulation. Our study underscores the importance of immune regulation in reproductive health and highlights IL-22 as a novel candidate for improving pregnancy outcomes in inflammatory conditions.