Immune-endocrine interactions in transgenic mice over expressing the TRH gene.

KLECHA, AJ; BARREIRO ARCOS, ML; GARCIA , SILVIA INES; PIROLA, CARLOS JOSE; GENARO, AM; CREMASCHI, GA

Rafain Palace Hotel and Convention Center, Foz do Iguacu. Brazil.

Congreso; Meeting of The Brazilian of Biochemistry and Molecular Biology Society (SBBq); 2010

Immune-endocrine interactions in transgenic mice over expressing the TRH gene. Klecha, A.J.1,2; Barreiro Arcos, M.L.2; Garcia, S.3; Pirola, C.3; Genaro, A.1,2; Cremaschi, G.1,2. 1CEFYBO-CONICET, 2Fac Farmacia y Bioquímica, UBA e 3IDIM-CONICET. We have previously demonstrated that thyroid axis status is able to modulate immunity. Thus, hypothyroidism induced in mice by propylthiouracil administration lead to a decrease in lymphocyte reactivity and in the secretion of the Th1 cytokines interferon-g (IFN-g) e interleukin-2 (IL-2). To investigate the participation of the different components of the axis, namely thyroid hormones (T3 and T4), thyrotropin (TSH) or thyrotropin realizing hormone (TRH), transgenic mice over-expressing the TRH gene (tm-TRH) were used to analyze lymphocyte activity. These animals were obtained by pronuclear injection of a gene construct containing the TRH precursor cDNA under the action of the CMV promoter and the polyadenylation signal of bovine growth hormone. The tm-TRH displayed higher diencephalic levels of TRH, but similar serum levels of TSH and thyroid hormones than control mice. TRH levels as well as TSH correlates with a higher T and B lymphocyte proliferative responses in response to selective mitogen stimulation. Additionally, these effects were accompanied by an increment in the release of Th1 cytokines and of IL-6, but not of other Th2 (IL-4 and IL-10) or the pro-inflammatory (TNF-a) cytokines. These results suggest that augmentation of hypothalamic-pituitary hormones leads to the increase of T and B cell responses, unlike the facts previously observed in hypothyroid conditions. Keywords: thyroid axis status, lymphocyte activity, cytokines.