Effect of β-Nicotinamide Adenine Dinucleotide on Acute Allograft Rejection After Rat Lung Transplantation.

UNLABELLED

Acute rejection is still a major limitation for a successful outcome in lung transplantation. Since (NAD) has been shown to have various immunomodulatory properties on the innate and adaptive immune system, we evaluate here a potential protective effect of NAD against acute lung rejection.

METHODS

Rat single-lung transplantation was performed in 2 groups (n = 8 per group), using Brown-Norway donors and major histocompatibility complex-mismatched Lewis recipients. Recipients of the NAD group received 1000 mg/kg NAD intraperitoneally before transplantation and daily thereafter until euthanasia, whereas the control group received saline solution. At autopsy on day 5, blood samples were analyzed and the lung allograft was assessed by bronchioalveolar lavage, histology, and immunochemistry.

RESULTS

The NAD group maintained an intact compliant lung tissue, a strong trend of lower acute cellular rejection (A3 versus A3-A4) and significantly less lymphocytic bronchiolitis (B0-B2R versus B1R-Bx). In addition, a trend of fewer alveolar CD68 macrophages and significantly fewer interstitial CD163 macrophages was observed. Bronchoalveolar lavage in the NAD group showed significantly fewer proinflammatory cytokines interleukin (IL)-6, IL-13, TNFα, and a protective IL-6/IL-10-ratio. In blood samples, we observed significantly fewer neutrophils, and proinflammatory GRO/KC in the NAD group.

CONCLUSIONS

NAD might be a promising substance in prevention of acute allograft rejection in lung transplantation.