TY - JOUR
T1 - Inhibition of concanavalin A-induced acute T cell dependent hepatic damage in mice by hypothyroidism
AU - Shirin, Haim
AU - Dotan, Iris
AU - Papa, Moshe
AU - Maaravi, Yoram
AU - Aeed, Husein
AU - Zaidel, Lillian
AU - Matas, Zipora
AU - Bruck, Rafael
AU - Moss, Steven F.
AU - Halpern, Zamir
AU - Oren, Ran
PY - 1999
Y1 - 1999
N2 - Aims/Background: Concanavalin A (Con A) activates T lymphocytes and causes acute T-cell-mediated hepatic injury in mice. Decreased thyroid hormonal production is associated with a variety of immunological manifestations, including inactivation of macrophages with reduced TNF production and reduced soluble IL-2 receptors in the serum. We have recently shown that hypothyroidism prevents the development of cirrhosis and also minimizes hepatic damage in rats with fulminant hepatic failure. In the present study we examined the effects of hypothyroidism on a mouse model of Con A induced T cell-mediated acute hepatitis. Methods: Hypothyroidism was induced both medically (MMI, PTU) and surgically. Eight groups of 10 mice each were studied: euthyroid controls (2 groups: water, Con A) and hypothyroid (6 groups: MMI, PTU, Surgical, MMI-Con A, PTU-Con A, Surgical-Con A). Results: Hepatic inflammation was significantly decreased in each of the Con A treated hypothyroid groups of mice. The serum transaminases, TNF-α and IL-6 levels were significantly elevated in the Con A treated group while near normal levels were found in the hypothyroid Con A treated groups (mean ± SE AST: 1499 ± 18 vs 78 ± 10 IU/l, p < 0.001; TNF: 2500 ± 250 vs 135 ± 15 pg/ml, p < 0.001, IL-6: 12,200 ± 300 vs 1260 ± 140 pg/ml, p < 0.001, respectively). Conclusions: Hypothyroidism, independent of the mode of induction, can effectively inhibit the development of acute T cell-mediated liver damage in mice. These results suggest that some decrease in thyroid function might have a role in the prevention of immune mediated liver diseases.
AB - Aims/Background: Concanavalin A (Con A) activates T lymphocytes and causes acute T-cell-mediated hepatic injury in mice. Decreased thyroid hormonal production is associated with a variety of immunological manifestations, including inactivation of macrophages with reduced TNF production and reduced soluble IL-2 receptors in the serum. We have recently shown that hypothyroidism prevents the development of cirrhosis and also minimizes hepatic damage in rats with fulminant hepatic failure. In the present study we examined the effects of hypothyroidism on a mouse model of Con A induced T cell-mediated acute hepatitis. Methods: Hypothyroidism was induced both medically (MMI, PTU) and surgically. Eight groups of 10 mice each were studied: euthyroid controls (2 groups: water, Con A) and hypothyroid (6 groups: MMI, PTU, Surgical, MMI-Con A, PTU-Con A, Surgical-Con A). Results: Hepatic inflammation was significantly decreased in each of the Con A treated hypothyroid groups of mice. The serum transaminases, TNF-α and IL-6 levels were significantly elevated in the Con A treated group while near normal levels were found in the hypothyroid Con A treated groups (mean ± SE AST: 1499 ± 18 vs 78 ± 10 IU/l, p < 0.001; TNF: 2500 ± 250 vs 135 ± 15 pg/ml, p < 0.001, IL-6: 12,200 ± 300 vs 1260 ± 140 pg/ml, p < 0.001, respectively). Conclusions: Hypothyroidism, independent of the mode of induction, can effectively inhibit the development of acute T cell-mediated liver damage in mice. These results suggest that some decrease in thyroid function might have a role in the prevention of immune mediated liver diseases.
KW - Acute hepatitis
KW - Concanavalin-A
KW - Hypothyroidism
UR - http://www.scopus.com/inward/record.url?scp=0032978510&partnerID=8YFLogxK
U2 - 10.1111/j.1478-3231.1999.tb00037.x
DO - 10.1111/j.1478-3231.1999.tb00037.x
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:0032978510
SN - 0106-9543
VL - 19
SP - 206
EP - 211
JO - Liver
JF - Liver
IS - 3
ER -