• Sarcoidosis

We thank Dr Brodlie and coworkers for their letter1 and fully agree on the necessity to evaluate whether cells other than lymphocytes and macrophages are involved in IL-17 release in sarcoid lungs. The main manifestation of sarcoidosis is an accumulation of mononuclear inflammatory cells, mostly CD4⁺ T cells and monocytes/macrophages in involved organs, including the lungs.2 As specified in our ‘Materials and methods’ section, we evaluated cells obtained by filtering bronchoalveolar lavage (BAL) fluid through gauze. A standard morphological and immunological analysis of BAL cellular components was performed. The analysis included cell recovery and differential count of macrophages, lymphocytes, neutrophils and eosinophils (table 1) coupled with a flow cytometry analysis of BAL cells.

Table 1 integrates information given in our published paper,2 clearly demonstrating that the number of BAL neutrophils was fair in our case series. This unfortunately prevented a definitive evaluation of whether polymorph nucleates represent a source of IL-17. Nonetheless, as shown in figure 1, in selected cases with a significant number of BAL neutrophils (two subjects) a certain degree of IL-17 expression was shown. Experiments are in progress in our lab aimed at evaluating the role of the IL-17 and neutrophil interaction in fibrogenic diffuse parenchymal lung disease (DPLD), including sarcoidosis. In fact, neutrophils are known to play a crucial role in alveolar injury mechanisms in idiopathic pulmonary fibrosis and other types of DPLD. Furthermore, it has recently been shown that Th17 cells and IL-17A favour the development of fibrosis in a murine model of bleomycin-induced pulmonary fibrosis.3 Finally, patients with idiopathic pulmonary fibrosis show high BAL levels of IL-17.3

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Figure 1

Analysis of IL-17 expression in neutrophils freshly obtained from the bronchoalveolar lavage (BAL) of two sarcoid patients (5% and 4% of BAL cells were neutrophils, respectively). Neutrophils were identified on the basis of CD16 positivity and morphological gating. As shown by the IL-17 staining profile, a faint positivity for the cytokine was detectable in both subjects.

Concerning putative mechanism through which IL-17 could in theory regulate neutrophil activation and recruitment, we are evaluating whether pulmonary IL-17 favours granulopoiesis in DPLD (via granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor)4 5 and induces neutrophil chemotaxis through stimulation of endothelial and epithelial cells. Nonetheless, it is important to note that IL-17 also has the capability of mediating neutrophil apoptosis and neutrophil phagocytosis through macrophages.6 Thus, since IL-17 regulates both recruitment and turnover of neutrophils, we are assessing whether lung IL-17 upmodulates or downmodulates neutrophils during the different phases of DPLD, including sarcoidosis.