Cytokine mRNA expression in postischemic/reperfused myocardium

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Inflammation Research

Background:

• The role of cytokines in skeletal muscle ischemia-reperfusion injury is known.
• Cytokine involvement in myocardial infarction and ischemia-reperfusion remains less understood.

Purpose of the Study:

• To investigate the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium.
• To localize interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) protein in the heart after ischemia-reperfusion.

Main Methods:

• Rats underwent permanent or temporary (35 min) LAD occlusion followed by reperfusion.
• Reverse transcriptase-polymerase chain reaction was used to quantify mRNA levels of TNF-alpha, IL-1 beta, IL-2, IL-6, IFN-gamma, and TGF-beta 1.
• Immunostaining localized IL-1 beta and TNF-alpha protein.

Main Results:

• Increased cardiac mRNA for most studied cytokines (except IL-6, IFN-gamma) was observed within 15-30 minutes of LAD occlusion, sustained for 3 hours.
• IL-6 and TGF-beta 1 mRNA levels were reduced during early reperfusion compared to permanent occlusion.
• Cytokine mRNA returned to baseline at 24 hours, with a secondary rise in IL-1 beta, TNF-alpha, and TGF-beta 1 at 7 days in permanently occluded animals.
• IL-1 beta and TNF-alpha proteins were found in microvasculature early post-reperfusion and in macrophages in healing infarct zones at 7 days.

Conclusions:

• Local cytokine gene expression occurs in postischemic myocardium.
• The regulation of local cytokine release is altered in the post-ischemic heart.
• Cytokines play a role in myocardial inflammation following ischemia and reperfusion.