Effects of 4-nonylphenol and/or diisononylphthalate on THP-1 cells: impact of endocrine disruptors on human immune system parameters.

The aim of the present work is to investigate the link between two endocrine disruptor compounds (EDCs), which are chemicals that interfere with the hormone system in human and wildlife, and the human immune response through a study of their effects on the THP-1 human cell line which was used as a model for macrophages. We used two EDCs, diisononylphthalate (DiP) and 4-n-nonylphenol (NP) alone or in combination in order to evaluate the effects of these compounds on several parameters of the immune response - cytokine secretion, phagocytosis and the putative implication of the estrogen receptors - by studying the level of MAPK activation. NP and DiP strongly reduced phagocytosis and modify cytokine secretions. Indeed, differentiated THP-1 cell exposures (i) to 5 and 10 microM of combination of NP and DiP induced an IL-8 level in the medium respectively of 28.9 and 45 percent higher than the level obtained for the control (untreated cells), (ii) to combination of NP and DiP at 10 microM induced an increase of IL-1β level in comparison to the control level, (iii) to combination of NP and DiP induced an increase of TNF-α level whatever the concentration of EDCs tested (between 0 and 10 microM). Lastly, differentiated THP-1 cell exposure to NP, DiP alone or in combination (2 microM for each condition) induced a decrease of ERK1/2 phosphorylation in comparison to ERK1/2 phosphorylation level of the control. Moreover, differentiated THP-1 cell treatments by ICI-182780 (an estrogen receptor antagonist) supressed the EDC effects on ERK1/2 phosphorylation level which indicates an estrogen receptor-dependent pathway. These results suggest that EDCs have the ability to alter the human immune function, maybe by interfering with endocrine balance.