Production of Interleukin 13 by Alveolar Macrophages from Normal and Fibrotic Lung

Abstract

Human interleukin 13 (IL-13) is a cytokine that has a profound effect on primary immune cells by inducing immunoglobulin production, proliferation of B cells, and the differentiation of cells of the monocytic lineage. IL-13 can inhibit the production of inflammatory cytokines by both macrophages and monocytes. Previously, IL-13 expression has been reported only in cells of the T-cell lineage and the mast cell line HMC-1. We now report the presence of IL-13 mRNA and protein in human alveolar macrophages (AMs) analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunoabsorbent assay (ELISA), respectively, and IL-13 protein in bronchoalveolar lavage fluid (BALF) of subjects with pulmonary fibrosis. We have investigated 13 patients from 49 to 75 yr of age with forms of pulmonary fibrosis, and eight healthy volunteers from 24 to 61 yr of age. Their AMs were obtained by bronchoalveolar lavage (BAL) and purified by adherence. The proportion of BAL purified AMs expressing IL-13 mRNA was increased in those subjects with fibrotic lung disease, in comparison with those from control subjects (11 of 13 versus 2 of 8, P < 0.01). IL-13 protein was detectable in the BALF of 8 of 13 patients with pulmonary fibrosis, but in none of the control subjects. AMs of four subjects with systemic sclerosis were cultured and IL-13 protein was increased in the culture supernatants when compared to the control subjects, although this did not reach significance. These findings show that IL-13 mRNA is not only a product of T cells, but is also expressed in both normal AMs and those from subjects with pulmonary fibrosis, and that at least some of the IL-13 mRNA is translated into protein and secreted in subjects with pulmonary fibrosis. We hypothesize that IL-13 may be expressed by normal human AMs as part of the homeostatic control process but its production may be increased in the presence of inflammatory lung disease.

IL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung

“…Exaggerated levels of IL-13 production have been implicated in the pathogenesis of a variety of disorders, including asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, scleroderma, hepatic fibrosis, and nodular sclerosing Hodgkin's disease (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). The remarkable effects that IL-13 can have in these disorders can be appreciated in studies that highlighted the ability of IL-13 to induce tissue inflammation, cathepsin-and MMP-mediated proteolysis, and TGF-␤1-induced tissue fibrosis (25,32,48).…”

Role of Early Growth Response-1 (Egr-1) in Interleukin-13-induced Inflammation and Remodeling

“…The latter is nicely illustrated in studies from our laboratory and others that demonstrate that IL-13 is a potent stimulator of eosinophil-, macrophage-and lymphocyte-rich inflammation, mucus metaplasia, tissue fibrosis, and parenchymal proteolysis (5)(6)(7). In accord with these observations, IL-13 dysregulation has been documented, and IL-13 has been implicated in the pathogenesis of a variety of diseases characterized by inflammation and tissue remodeling including asthma, scleroderma, idiopathic pulmonary fibrosis, viral pneumonia, hepatic fibrosis, nodular sclerosing Hodgkin's disease, and chronic obstructive pulmonary diseases (COPD) (1)(2)(3)(4)(7)(8)(9)(10)(11)(12)(13). Studies from our laboratory and others have demonstrated that IL-13 mediates its tissue effects by activating a broad array of downstream target genes including chemokines, matrix metalloproteinases (MMPs), transforming growth factor (TGF)-␤ 1 , and chitinases (6, 14 -17).…”

“…Subsequent studies demonstrated that IL-13 and IL-4 play distinct roles in biology with IL-4 contributing to Th2 cell differentiation and response generation, whereas IL-13 contributes as a major effector of Th2 inflammation and tissue remodeling (1)(2)(3)(4). The latter is nicely illustrated in studies from our laboratory and others that demonstrate that IL-13 is a potent stimulator of eosinophil-, macrophage-and lymphocyte-rich inflammation, mucus metaplasia, tissue fibrosis, and parenchymal proteolysis (5)(6)(7). In accord with these observations, IL-13 dysregulation has been documented, and IL-13 has been implicated in the pathogenesis of a variety of diseases characterized by inflammation and tissue remodeling including asthma, scleroderma, idiopathic pulmonary fibrosis, viral pneumonia, hepatic fibrosis, nodular sclerosing Hodgkin's disease, and chronic obstructive pulmonary diseases (COPD) (1)(2)(3)(4)(7)(8)(9)(10)(11)(12)(13).…”

TNFα, interleukin-10 and interleukin-18 expression in cells of the bronchoalveolar lavage in patients with pulmonary complications following bone marrow or peripheral stem cell transplantation: a preliminary study

“…Ratios of IL-18:␤-actin, TNF␣:␤-actin and IL-10:␤-actin were calculated for semiquantitative RNA expression analysis as previously described. 20 …”