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Correspondence |

Interleukin-17 and Neutrophils Are Increased in BAL Fluid During Acute Lung RejectionResponse FREE TO VIEW

Geert M. Verleden, MD, PhD; Robin Vos, MD; Bart M. Vanaudenaerde; Dirk Van Raemdonck, MD, PhD; Lieven J. Dupont, MD, PhD
Author and Funding Information

Affiliations: University Hospital Gasthuisberg, Leuven, Belgium,  University of Chicago Hospital, Chicago, IL

Correspondence to: Geert M. Verleden, University Hospital Gasthuisberg, Lung Transplantation Unit, 49 Herestraat, B-3000 Leuven, Belgium; e-mail: geert.verleden@uz.kuleuven.be



Chest. 2007;131(6):1988-1989. doi:10.1378/chest.07-0473
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Recently, Bhorade et al1 showed that there is an up-regulation of interleukin (IL)-15 protein in BAL fluid in lung transplant patients with acute rejection receiving the IL-2 blocking agent daclizumab. This is a very interesting finding; however, we can hardly agree with their results of BAL fluid cellular analysis. In fact, using 90 mL of normal saline solution, they found in the BAL cellular differentiation higher percentages of neutrophils and lymphocytes in the control patients compared to the rejectors (17% and 14%, respectively, compared to 9% and 9%). Moreover, there must be a mistake in the percentages because they add up to > 100%.1Although these results were not significantly different between groups, they are quite unusual. Indeed, several authors have shown that acute cellular rejection represents a lymphocytic perivascular infiltration with an increase in BAL lymphocytes,2which also correlates with the severity of acute rejection.3We have recently published a study4 in patients with acute lung rejection in which we corroborated these results, but we were also able to demonstrate an increased level of IL-17 protein in their BAL fluid, and this was accompanied by an increased BAL neutrophilia, which also correlated with the severity of the acute rejection. At the same time, there was an increase in IL-8 protein in the BAL fluid that correlated with the BAL neutrophilia.4As a consequence, we hypothesized that IL-17, which may stimulate airway epithelial and smooth-muscle cells to release Il-8,5 is indirectly responsible for the BAL neutrophilia during acute rejection. This is in contradiction to what the authors demonstrate in the present study.1 We would like to ask the authors how they could explain their current BAL fluid cellular differential results in view of our recent findings?

The authors have no conflicts of interest to disclose.

The authors have no conflicts of interest to disclose.

Bhorade, SM, Yu, A, Vigneswaran, WT, et al (2007) Elevation of interleukin-15 protein expression in bronchoalveolar fluid in acute lung allograft rejection.Chest131,533-538. [PubMed] [CrossRef]
 
Slebos, D, Postma, DS, Koeter, GH, et al Bronchoalveolar lavage fluid characteristics in acute and chronic lung transplant rejection.J Heart Lung Transplant2004;23,532-540. [PubMed]
 
De Hoyos, A, Chamberlain, D, Schvartzman, R, et al Prospective assessment of a standardized pathologic grading system for acute rejection in lung transplantation.Chest1993;103,1813-1818. [PubMed]
 
Vanaudenaerde, BM, Dupont, LJ, Wuyts, WA, et al The role of interleukin-17 during acute rejection after lung transplantation.Eur Respir J2006;27,779-787. [PubMed]
 
Vanaudenaerde, BA, Wuyts, WA, Dupont, LJ, et al Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cellsin vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome.J Heart Lung Transplant2003;22,1280-1283. [PubMed]
 
To the Editor:

We appreciate the interest that Verleden and colleagues have expressed in our article1(February 2007) that demonstrated an elevation in BAL interleukin-15 levels in lung transplant recipients with acute rejection. They comment that the BAL fluid cellularity and differential in our patients was discrepant from their results that have shown an increase in the percentage of lymphocytes and neutrophils in BAL from lung transplants with acute rejection.2 While there have been several reports23 suggesting BAL lymphocytosis in acute rejection, BAL cellularity in lung transplant recipients may be affected by several clinical conditions, including the severity of acute rejection grade, the temporal relation to organ engraftment, concomitant infections or colonization with organisms (bacterial, viral, fungal), and current immunosuppression. In addition, BAL cell differentials vary among studies depending on the method of BAL fluid collection. These inconsistencies in BAL cellularity in acute lung allograft rejection have been previously described,25 as noted by Verleden and colleagues. As a result, there are several plausible reasons for the differences in BAL cellularity in our study: (1) the majority of our patients had minimal grade rejection (A1), which may lead to a decrease percentage of lymphocytes; (2) we did not exclude patients with colonization or coinfection with pathogens that may have affected the BAL cell differentials (logistic regression analysis showed that this did not affect BAL interleukin-15 levels); (3) given the redundancy of the immune system and the timing of cellular events in the development of rejection, there are probably several different mechanisms by which rejection occurs (that may not be addressed by a single time point BAL sampling). We would like to thank the authors for noting that in Table 4, the BAL fluid cell counts for the control group variable “Other” should be 7% instead of 17%.1

References
Bhorade, SM, Yu, A, Vigneswaran, W, et al Elevation interleukin-15 protein expression bronchoalveolar fluid in acute lung allograft rejection.Chest2007;131,533-538. [PubMed] [CrossRef]
 
Vanaudenaerde, BM, Dupont, LJ, Wuyts, WA, et al The role of interleukin-17 during acute rejection after lung transplantation.Eur Respir J2006;27,779-787. [PubMed]
 
Slebos, D, Postma, DS, Koeter, GH, et al Bronchoalveolar lavage fluid characteristics in acute and chronic lung transplant rejection.J Heart Lung Transplant2004;23,532-540. [PubMed]
 
Laan, M, Linden, A, Riise, GC, et al IL-16 in the airways of lung allograft recipient with acute rejection or obliterative bronchiolitis.Clin Exp Immunol2003;133,290-296. [PubMed]
 
Whitehead, BF, Stoehr, C, Finkle, C, et al Analysis of bronchoalveolar lavage from human lung transplant recipients by flow cytometry.Respir Med1995;89,27-34. [PubMed]
 

Figures

Tables

References

Bhorade, SM, Yu, A, Vigneswaran, WT, et al (2007) Elevation of interleukin-15 protein expression in bronchoalveolar fluid in acute lung allograft rejection.Chest131,533-538. [PubMed] [CrossRef]
 
Slebos, D, Postma, DS, Koeter, GH, et al Bronchoalveolar lavage fluid characteristics in acute and chronic lung transplant rejection.J Heart Lung Transplant2004;23,532-540. [PubMed]
 
De Hoyos, A, Chamberlain, D, Schvartzman, R, et al Prospective assessment of a standardized pathologic grading system for acute rejection in lung transplantation.Chest1993;103,1813-1818. [PubMed]
 
Vanaudenaerde, BM, Dupont, LJ, Wuyts, WA, et al The role of interleukin-17 during acute rejection after lung transplantation.Eur Respir J2006;27,779-787. [PubMed]
 
Vanaudenaerde, BA, Wuyts, WA, Dupont, LJ, et al Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cellsin vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome.J Heart Lung Transplant2003;22,1280-1283. [PubMed]
 
Bhorade, SM, Yu, A, Vigneswaran, W, et al Elevation interleukin-15 protein expression bronchoalveolar fluid in acute lung allograft rejection.Chest2007;131,533-538. [PubMed] [CrossRef]
 
Vanaudenaerde, BM, Dupont, LJ, Wuyts, WA, et al The role of interleukin-17 during acute rejection after lung transplantation.Eur Respir J2006;27,779-787. [PubMed]
 
Slebos, D, Postma, DS, Koeter, GH, et al Bronchoalveolar lavage fluid characteristics in acute and chronic lung transplant rejection.J Heart Lung Transplant2004;23,532-540. [PubMed]
 
Laan, M, Linden, A, Riise, GC, et al IL-16 in the airways of lung allograft recipient with acute rejection or obliterative bronchiolitis.Clin Exp Immunol2003;133,290-296. [PubMed]
 
Whitehead, BF, Stoehr, C, Finkle, C, et al Analysis of bronchoalveolar lavage from human lung transplant recipients by flow cytometry.Respir Med1995;89,27-34. [PubMed]
 
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