Inhibition of concanavalin A-induced acute T cell dependent hepatic damage in mice by hypothyroidism.
OBJECTIVE
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-alpha 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.
Department of Gastroenterology, The E. Wolfson Medical Center, Holon, Israel.
H
H
Shirin
I
I
Dotan
M
M
Papa
Y
Y
Maaravi
H
H
Aeed
L
L
Zaidel
Z
Z
Matas
R
R
Bruck
S F
SF
Moss
Z
Z
Halpern
R
R
Oren
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003208:Concanavalin A / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000097:blood; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D007111:Immunity, Cellular / Q000276:immunology; D007249:Inflammation / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008713:Methimazole; D051379:Mice; D008807:Mice, Inbred BALB C; D011441:Propylthiouracil; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013965:Thyroidectomy; D013997:Time Factors
D016207:Cytokines; D003208:Concanavalin A; D008713:Methimazole; D011441:Propylthiouracil; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase