Both tacrolimus and sirolimus decrease Th1/Th2 ratio, and increase regulatory T lymphocytes in the liver after...

Area of Science:

• Immunology
• Hepatology
• Transplantation

Background:

• Ischemia/reperfusion (I/R) injury is a significant clinical challenge.
• Immunosuppressants are known to mitigate I/R injury, but the precise mechanisms are not fully understood.
• T lymphocytes play a critical role in the inflammatory response following I/R.

Purpose of the Study:

• To investigate the effects of tacrolimus and sirolimus on lymphocyte subpopulations in a rat model of hepatic I/R injury.
• To elucidate the role of T lymphocyte modulation in the protective effects of these immunosuppressants against I/R injury.

Main Methods:

• A rat model of hepatic I/R injury was established.
• Animals were treated with tacrolimus, sirolimus, or vehicle.
• Lymphocyte subpopulations, including T lymphocytes (Th1, Th2, Tregs), were analyzed using flow cytometry.
• Liver injury markers such as plasma lactate dehydrogenase (LDH) and histological damage were assessed.

Main Results:

• I/R injury led to increased mortality, liver damage, and infiltration of immune cells.
• Both tacrolimus and sirolimus significantly reduced I/R-induced liver injury and mortality.
• Immunosuppressants reverted the increased Th1/Th2 ratio and increased the proportion of regulatory T lymphocytes (Tregs) in I/R livers.
• The protective effects correlated with a decreased ratio of pro-inflammatory to anti-inflammatory T lymphocytes and an increased Treg proportion.

Conclusions:

• Tacrolimus and sirolimus exert protective effects against hepatic I/R injury, partly through modulation of T lymphocyte populations.
• The balance between pro-inflammatory and anti-inflammatory T lymphocytes, particularly the increase in Tregs, is a key mechanism underlying immunosuppressant-mediated protection in I/R injury.