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.


CONCLUSIONS
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.
Bhorade
Sangeeta M
SM
Department of Medicine, University of Chicago, Chicago, USA. sbhorade@medicine.bsd.uchicago.edu
Yu
Andrew
A
Vigneswaran
Wickii T
WT
Alex
Charles G
CG
Garrity
Edward R
ER
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy; D000077561:Daclizumab; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019409:Interleukin-15 / Q000032:analysis*; D007376:Interleukin-2 / Q000032:analysis*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D000077561:Daclizumab