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Houdeau, E. et al.

Houdeau, Moriez, Leveque, Salvador-Cartier, Waget, Leng, Bueno, Bucala, Fioramonti,

Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat.

Background & Aims: Sex steroids influence IBD symptoms. Macrophage migration inhibitory factor ( MIF), a target of sex steroids in other inflammatory models, promotes interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha release in colitis. We investigated whether estradiol and progesterone influence MIF, IL-1beta, and TNF-alpha production in experimental colitis. Methods: Colonic MIF, IL-1beta, and TNF-alpha levels were measured in cyclic and ovariectomized rats, with or without estradiol benzoate (EB) or progesterone ( P) replacement. MIF distribution was assessed by immunohistochemistry. Cytokines, myeloperoxidase activity, macroscopic damage, and plasma corticosterone were assessed 24 hours after intrarectal trinitrobenzene sulfonic acid (TNBS), with and without neutralizing anti- MIF antibody. Effects of EB and P on myeloperoxidase activity and MIF concentration were also assessed at 7 days in dextran sulfate sodium-induced colitis. Results: Basal IL-1beta and TNF-alpha contents did not fluctuate during the estrous cycle, while MIF concentrations increased from estrus (estrogen dominance) to metestrus ( P dominance; P < .05). EB and P treatment mimicked these effects in ovariectomized rats, and similarly altered MIF immunostaining. Progesterone dominance aggravated TNBS colitis in comparison with estrogen. Progesterone enhanced TNBS-induced MIF ( P < .001) and TNF-alpha ( P < .01) production, while EB decreased MIF ( P < .01) and IL-beta levels ( P < .01). Anti- MIF antibody prevented P- mediated up-regulation of TNF-alpha, improved TNBS colitis, and enhanced plasma corticosterone. At 7 days after dextran sulfate sodium, EB decreased myeloperoxidase activity and MIF concentration, while P had no effect. Conclusions: Estrogen decreases while progesterone increases MIF production in the female rat colon. Changes in basal MIF contents may affect colon susceptibility to inflammation, by modulating TNF-alpha and IL-1beta production during early stages of colitis.[1]

References

Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat. Houdeau, E., Moriez, R., Leveque, M., Salvador-Cartier, C., Waget, A., Leng, L., Bueno, L., Bucala, R., Fioramonti, J. Gastroenterology (2007) [Pubmed]

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