Pro-inflammatory effects of all-trans retinoic acid in experimental acute inflammation - insights into eosinophil and neutrophil dynamics.

CONTEXT: All-trans retinoic acid (ATRA), a metabolite of vitamin A, regulates embryogenesis, regeneration, hematopoiesis, differentiation, and apoptosis. It also exerts immunomodulatory effects and is used in inflammatory disease models.

OBJECTIVE

This study aimed to investigate the paradoxical pro-inflammatory effects of ATRA on eosinophil and neutrophil recruitment and activation.

MATERIALS AND

METHODS

We used thioglycolate- and zymosan-induced peritonitis models in mice to evaluate leukocyte recruitment following ATRA treatment. The roles of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF), and the 5-lipoxygenase (5-LO) pathway were assessed using genetically deficient mice and pharmacological inhibitors.

RESULTS AND DISCUSSION: ATRA increased total leukocyte, eosinophil, and neutrophil counts in peritoneal exudates, enhancing the response to both thioglycolate and zymosan. The effects were microenvironment-dependent and likely mediated by local release of pro-inflammatory cytokines and chemokines. iNOS was required for eosinophil recruitment, while TNF contributed to both eosinophil and neutrophil recruitment. The 5-LO pathway was essential for eosinophil involvement. These findings suggest that ATRA can paradoxically enhance inflammation by modulating innate immune cell responses.

CONCLUSIONS

ATRA promotes inflammation through iNOS, TNF, and 5-LO-dependent pathways, revealing complex mechanisms of immune modulation with potential relevance for inflammatory disease management.