Related Experiment Video
Updated: Aug 13, 2026
Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
Heart allograft protection with low-dose carbon monoxide inhalation: effects on inflammatory mediators and
Atsunori Nakao1, Hideyoshi Toyokawa, Masanori Abe
1Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Background:
Carbon monoxide (CO), a byproduct of heme catalysis, has lately received considerable attention as a regulatory molecule in cellular and biological processes. CO has been shown to provide potent protection against a variety of tissue injuries. We hypothesized in this study that low concentration CO would be beneficial for organ allografts, which frequently undergo several types of injury such as ischemia/reperfusion, alloimmune reaction, and inflammation
Methods:
The efficacy of low-dose CO was examined in a fully allogeneic LEW to BN rat heterotopic heart transplantation (HHTx) model. Recipients were kept in air or exposed to low-dose CO (20 ppm) for 14, 28, or 100 days after HHTx under short-course tacrolimus
Results:
CO treatment (d0-28, 0-100) was remarkably effective in prolonging heart allograft survival to a median of >100 from 45 days in the air-control group, with significant reductions of arteritis, fibrosis, and cellular infiltration, including macrophages and T cells. CO inhibited intragraft upregulation of Th1 type cytokines (IL-2, IFNgamma), proinflammatory mediators (IL-1beta, TNFalpha, IL-6, COX-2), and adhesion molecule. Shorter CO exposure in early (0-13d) and late (14-28d) posttransplant periods also prolonged graft survival, with a significant inhibition of inflammatory mediators
Conclusions:
These results show that low dose CO inhalation protects heart allografts and can considerably prolong their survival. CO appears to function via multiple mechanisms, including direct inhibition of Th1 type cytokine production and regulation of inflammatory responses.
