"CYTOKINE PRODUCTION AND T LYMPHOCYTE INFILTRATION IN UTERINE TISSUE OF HYPERANDROGENIZED MICE"

EVELIN MARIEL ELIA; EDUARDO LOMBARDI; GUILLERMO DI GIROLAMO; CLAUDIO GONZALEZ; ALICIA BEATRIZ MOTTA

Miami, Florida, USA

Congreso; Inter American Society of Hipertensión and Consortium for Southeastern Hipertensión control Joint Meeting; 2007

Inter American Society of Hipertensión and Consortium for Southeastern Hipertensión

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder generally associated with hyperandrogenism, recurrent miscarriage, insulin resistance and hypertension. T lymphocytes (LT) play a role in the local pathological mechanisms of PCOS and several studies have shown and altered secretion of cytokines in this syndrome. An inflammatory status increases the risk of cardiovascular disease and hypertension. OBJETIVE: To evaluate the inflammatory status in hyperandrogenized mice as well as the LT infiltration in uterus. METHODS: Female prepuberal mice BALB/c were daily (during 20 days) injected with DHEA [6 mg/100 g body weight (BW): D group)]. Animals of the D+M group were injected with DHEA and given metformin(M) orally (50 mg/100 g BW). C group consisted of animals injected with oil and given water orally. The M group was mice treated orally with M. Cytokine levels (IFN-gama, IL-2, IL-4 and IL-10) were evaluated by Elisa Tests and the LT infiltration was analyzed by inmunostainig. RESULTS: D diminished the LT CD4+ infiltration in uterus(C: 2.16±0.23 arbitrary units vs D: 0.55±0.12 au, M: 0.27±0.05 au, D+M: 0.27±0.05 au) and of T CD8+ (C: 3.58±0.05 au vs D: 0.33±0.03 au, M: 2.81±0.11 au, D+M:  0.36±0.08 au) respect controls, while D+M was not able to revert this effect. More over, D produced the subtype LT CD4+ mastery (LT CD8+/LT CD4+: 1. 6 for C and 0. 6 for D). This  was reverted by  D+M (1.3). D significantly increased the secretion of IFN-gama (C: no detectable (ND), M: ND, D: 19.76±3.74 pg/ml, D+M: ND), IL-4 (C: ND, M: ND, D: 8.94±4.01 pg/ml, D+M: ND) and IL-10 (C: ND, M: 17.33±9.72 pg/ml, D: 90.67±18.19 pg/ml, D+M: 54±12.03 pg/ml) respect controls. While D+M significantly diminished this pattern. The IL-2 secretion was not altered significantly by the treatments but showed a tendency similar than IFN-gama, IL-4 and IL-10. (C: 3.59±1.11 pg/ml, M: 4.61±1.40 pg/ml, D: 4.89±2.03 pg/ml, D+M: 3.5±1.22 pg/ml) CONCLUSIONS: The hyperandrogenization with D produced the inversion of the LT subtype that predominate in uterus and on the other hand produced an increased secretion of cytokines. This augmented secretion of cytokines may be the result of the alteration in the LT infiltration in the different tissues. Here we show the alteration in the LT population in uterus and several studies have shown this alteration in other tissues, like ovaries. D+M treatment was able to modify these effects.