Elevation of Interleukin-15 Protein Expression in Bronchoalveolar Fluid in Acute Lung Allograft Rejection

Background:Acute rejection remains a major source of morbidity in lung transplantation. Although interleukin (IL)-2 has been the principal T-cell growth factor implicated in acute rejection, IL-2 blockade does not prevent acute rejection completely. Recently, IL-15, a stromal cell-derived cytokine, has been found to share a similar biological function with IL-2. We hypothesized that IL-15 levels may be elevated in acute lung rejection in the presence of IL-2 blockade.Methods:Acute allograft rejection developed in 21 of 42 lung transplant recipients. BAL fluid (BALF) was analyzed for IL-2 and IL-15 protein expression by standard enzyme-linked immunosorbent assay.Results:The average (± SD) BALF IL-15 level was higher in lung transplant recipients with acute rejection compared to those without rejection (25 ± 25 pg/mL vs 4.5 ± 1.5 pg/mL, respectively; p < 0.0001). In addition, there appeared to be a bimodal distribution of BALF IL-15 levels in lung transplant recipients with acute rejection. BALF IL-2 levels were not associated with acute rejection. BALF IL-15 levels were not associated with bacterial, fungal, or cytomegalovirus infection.Conclusion:These data show that BALF IL-15 levels are elevated in acute lung allograft rejection in the presence of IL-2 receptor blockade and may be an important mediator for acute rejection in lung transplantation.