BACKGROUND:Interleukin-17 (IL-17) is a pro-inflammatory cytokine produced from CD4+ T cells and is associated with neutrophilia in infection, ischemia-reperfusion injury, and possibly acute and chronic rejection (bronchiolitis obliterans syndrome, or BOS) after lung transplantation (LTx). Everolimus (ERL) decreases acute rejection, possibly via decreasing airway CD4+ cells and neutrophils. This prospective study aims to assess: (1) the possible role of IL-17 as a link between LTx clinical outcomes (such as infection, acute rejection and BOS) and airway immunopathologic measures from endobronchial biopsy (EBB) and bronchoalveolar lavage (BAL); and (2) any differences in IL-17 production between ERL and azathioprine (AZA)-based immunosuppression. METHODS: This sub-study, from a larger, prospective clinical ERL vs AZA randomized, controlled trial, examines EBB IL-17 expression, relating this to clinical outcomes, BAL and EBB cell counts. EBBIL-17 staining was measured by immunohistologic techniques and expressed as cells per square millimeter of lamina propria. RESULTS:Thirty-four LTx patients were randomized in a double-blind study (ERL = 19, AZA = 15) and underwent a total of 113 bronchoscopies over a 3-year follow-up period. Twenty-six EBBs were taken from LTx recipients with BOS of at least Grade 0p (10 patients). Univariate associations correlated IL-17 positively with EBB CD8+ cells (R2 = 0.010, p = 0.001) and negatively with days post-LTx (R2 = 0.07, p = 0.002). In a multivariate model, IL-17 variability was explained by: days post-LTx (6.2%, p = 0.02); EBB CD8+ (5.9%, p = 0.02); cytomegalovirus mismatch (6.1%, p = 0.02); BAL lymphocyte percentage (4.2%, p = 0.05); and clinical infection (3.7%, p = 0.06). CONCLUSIONS: IL-17 is associated with the early post-LTx time period and airway CD8+ cells. Unexpectedly, rejection grade, BOS, BAL IL-8 andneutrophil counts are not associated. ERL appears not to directly affect IL-17, despite its effects on CD4 cells.
RCT Entities:
BACKGROUND:Interleukin-17 (IL-17) is a pro-inflammatory cytokine produced from CD4+ T cells and is associated with neutrophilia in infection, ischemia-reperfusion injury, and possibly acute and chronic rejection (bronchiolitis obliterans syndrome, or BOS) after lung transplantation (LTx). Everolimus (ERL) decreases acute rejection, possibly via decreasing airway CD4+ cells and neutrophils. This prospective study aims to assess: (1) the possible role of IL-17 as a link between LTx clinical outcomes (such as infection, acute rejection and BOS) and airway immunopathologic measures from endobronchial biopsy (EBB) and bronchoalveolar lavage (BAL); and (2) any differences in IL-17 production between ERL and azathioprine (AZA)-based immunosuppression. METHODS: This sub-study, from a larger, prospective clinical ERL vs AZA randomized, controlled trial, examines EBB IL-17 expression, relating this to clinical outcomes, BAL and EBB cell counts. EBB IL-17 staining was measured by immunohistologic techniques and expressed as cells per square millimeter of lamina propria. RESULTS: Thirty-four LTx patients were randomized in a double-blind study (ERL = 19, AZA = 15) and underwent a total of 113 bronchoscopies over a 3-year follow-up period. Twenty-six EBBs were taken from LTx recipients with BOS of at least Grade 0p (10 patients). Univariate associations correlated IL-17 positively with EBB CD8+ cells (R2 = 0.010, p = 0.001) and negatively with days post-LTx (R2 = 0.07, p = 0.002). In a multivariate model, IL-17 variability was explained by: days post-LTx (6.2%, p = 0.02); EBB CD8+ (5.9%, p = 0.02); cytomegalovirus mismatch (6.1%, p = 0.02); BAL lymphocyte percentage (4.2%, p = 0.05); and clinical infection (3.7%, p = 0.06). CONCLUSIONS:IL-17 is associated with the early post-LTx time period and airway CD8+ cells. Unexpectedly, rejection grade, BOS, BAL IL-8 and neutrophil counts are not associated. ERL appears not to directly affect IL-17, despite its effects on CD4 cells.
Authors: Zequan Yang; Ashish K Sharma; Joel Linden; Irving L Kron; Victor E Laubach Journal: J Thorac Cardiovasc Surg Date: 2009-03 Impact factor: 5.209
Authors: Thomas J Scriba; Barbara Kalsdorf; Deborah-Ann Abrahams; Fatima Isaacs; Jessica Hofmeister; Gillian Black; Hisham Y Hassan; Robert J Wilkinson; Gerhard Walzl; Sebastian J Gelderbloem; Hassan Mahomed; Gregory D Hussey; Willem A Hanekom Journal: J Immunol Date: 2008-02-01 Impact factor: 5.422