Cytokine and chemokine dysregulation by Endocrine Disrupting Chemicals (EDCs).

Abstract

Endocrine-disrupting chemicals (EDCs) are traditionally defined by their ability to interfere with hormonal signalling. However, increasing evidence indicates that their biological effects also involve interactions with the immune system, particularly through the modulation of cytokine and chemokine networks. This review examines the relationship between EDC exposure and cytokine and chemokine dysregulation across major classes of endocrine disruptors, considering evidence from in vitro, in vivo, and epidemiological studies. Overall, EDCs can alter the production and regulation of inflammatory and immunoregulatory cytokines and chemokines, including mediators involved in both acute and chronic inflammatory responses. Depending on the chemical and exposure context, these alterations may result in either enhanced inflammatory signalling or suppression of immune responses. Importantly, cytokine dysregulation does not appear to represent an isolated effect of EDC exposure, but may be part of a broader interaction between endocrine and immune signalling. Changes in cytokine activity can, in turn, affect endocrine pathways and tissue homeostasis, suggesting a potentially bidirectional relationship between hormonal and immune regulation. These responses are highly dependent on the specific chemical, dose, exposure duration, tissue, developmental stage, and biological context. Although cytokine/chemokine alterations are consistently reported, direct evidence that these alterations mediate endocrine or systemic outcomes remains limited. A better understanding of this endocrine-immune interaction may provide a broader framework for interpreting the systemic effects of EDC exposure and for assessing endocrine disruption beyond conventional hormonal endpoints.