H-P Hauber1, D Gholami, A Meyer, A Pforte. 1. Department of Internal Medicine, University Hospital Eppendorf, Hamburg, Germany. hans-peter.hauber@mcgill.ca
Abstract
BACKGROUND: Sarcoidosis is a systemic granulomatous disorder of unknown origin. Lymphocytic inflammation is dominated by expression of Th1 type cytokines such as tumour necrosis factor alpha (TNFalpha). Interleukin 13 (IL-13) is a Th2 cytokine which is expressed by CD4+ T cells and has been shown to suppress TNFalpha in human blood monocytes. The role of IL-13 as a possible anti-inflammatory cytokine in sarcoidosis was investigated. METHODS: mRNA expression of IL-13, IL-4, IL-10, and TNFalpha in bronchoalveolar lavage (BAL) fluid cells and peripheral mononuclear blood cells (PBM) of 18 patients with sarcoidosis and nine healthy controls was assessed using RT-PCR. In addition, IL-13 protein levels in BAL cell culture supernatants from 12 patients and all controls were measured and immunocytochemistry of IL-13 protein was performed in BAL fluid cells of eight patients. TNFalpha concentrations were measured with and without stimulation with recombinant human (rh) IL-13, rhIL-10, and lipopolysaccharide (LPS). RESULTS: IL-13 mRNA expression was significantly increased in BAL cells and PBM of patients compared with controls (p<0.05). No significant difference was found in IL-4 mRNA or IL-10 mRNA expression in BAL fluid cells or PBM between the two groups. TNFalpha mRNA expression was significantly higher in BAL fluid cells of patients than controls (p<0.05). IL-13 protein levels in BAL cell culture supernatants were slightly raised in half the patients investigated but in only two controls. Immunocytochemistry detected IL-13 protein in alveolar macrophages of patients. IL-13 led to decreased TNFalpha concentrations (p<0.05). CONCLUSIONS: IL-13 expression is increased in BAL cells and PBM in sarcoidosis and IL-13 is secreted from BAL cells. Alveolar macrophages may be the cellular source. These data suggest that IL-13 might have an anti-inflammatory effect by acting on TNFalpha.
BACKGROUND:Sarcoidosis is a systemic granulomatous disorder of unknown origin. Lymphocytic inflammation is dominated by expression of Th1 type cytokines such as tumour necrosis factor alpha (TNFalpha). Interleukin 13 (IL-13) is a Th2 cytokine which is expressed by CD4+ T cells and has been shown to suppress TNFalpha in human blood monocytes. The role of IL-13 as a possible anti-inflammatory cytokine in sarcoidosis was investigated. METHODS: mRNA expression of IL-13, IL-4, IL-10, and TNFalpha in bronchoalveolar lavage (BAL) fluid cells and peripheral mononuclear blood cells (PBM) of 18 patients with sarcoidosis and nine healthy controls was assessed using RT-PCR. In addition, IL-13 protein levels in BAL cell culture supernatants from 12 patients and all controls were measured and immunocytochemistry of IL-13 protein was performed in BAL fluid cells of eight patients. TNFalpha concentrations were measured with and without stimulation with recombinant human (rh) IL-13, rhIL-10, and lipopolysaccharide (LPS). RESULTS:IL-13 mRNA expression was significantly increased in BAL cells and PBM of patients compared with controls (p<0.05). No significant difference was found in IL-4 mRNA or IL-10 mRNA expression in BAL fluid cells or PBM between the two groups. TNFalpha mRNA expression was significantly higher in BAL fluid cells of patients than controls (p<0.05). IL-13 protein levels in BAL cell culture supernatants were slightly raised in half the patients investigated but in only two controls. Immunocytochemistry detected IL-13 protein in alveolar macrophages of patients. IL-13 led to decreased TNFalpha concentrations (p<0.05). CONCLUSIONS:IL-13 expression is increased in BAL cells and PBM in sarcoidosis and IL-13 is secreted from BAL cells. Alveolar macrophages may be the cellular source. These data suggest that IL-13 might have an anti-inflammatory effect by acting on TNFalpha.
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