Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, which has been implicated in the pathogenesis of fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the clinical significance of the serum VEGF level for evaluating disease severity and progression. The levels of VEGF in serum were measured in 41 patients with IPF, 14 patients with lung cancer, and 43 healthy volunteers. We measured the serum levels of CRP, LDH, KL-6, SP-D, and the parameters obtained from arterial blood gas analysis and pulmonary function tests. High-resolution computed tomography (HRCT) was performed to determine the extent of the interstitial and the alveolar opacities. The ability of each biomarker to predict disease severity was estimated by measuring the area under the receiver operating characteristic curve (AUC). The VEGF levels of IPF patients with high alveolar-arterial difference of oxygen (AaDO(2)) levels were significantly elevated than those with low AaDO(2) levels and those of healthy volunteers. When examined within the IPF group, a significant positive correlation was found between the VEGF levels and the HRCT interstitial score (p = 0.027) and the KL-6 levels (p = 0.037). Among several serum biomarkers, VEGF showed the largest AUC for predicting disease severity as defined by a high AaDO(2) value. There was an inverse correlation between the baseline VEGF level and the monthly change in percent predicted vital capacity. The serum VEGF level may reflect the severity of IPF and offer clinical benefits to predict the disease's progression.

Thymus- and activation-regulated chemokine (TARC/CCL17) is a lymphocyte-directed CC chemokine, which plays a role in the recruitment of CC chemokine receptor-4 positive T helper 2 (Th2) cells. In this study, we measured concentrations of TARC and Th2 cell-derived cytokines in bronchoalveolar lavage (BAL) fluid, as well as TARC concentrations in serum from patients with eosinophilic pneumonia and other interstitial lung diseases. TARC was significantly elevated in BAL fluids from patients with eosinophilic pneumonia (median, 240 pg/ml), whereas TARC was undetectable (< 7 pg/ml) in most cases of hypersensitivity pneumonitis, sarcoidosis, and idiopathic pulmonary fibrosis, as well as in healthy control subjects. Also, when present, quantities were less than 20 pg/ml. Elevated concentrations of interleukin (IL)-4, IL-5, and IL-13 were also detected in BAL fluid from patients with eosinophilic pneumonia. Interestingly, TARC concentrations in BAL fluids were closely correlated with the concentrations of IL-5 and IL-13. A serial examination showed that elevated TARC in BAL fluid rapidly fell to below detectable limits preceding decreases in IL-5 concentration and eosinophil percentage. Our results, in concordance with previous studies, demonstrate the potential activity of TARC for recruiting Th2 cells to the lungs and suggest a significant role for TARC in the pathogenesis of eosinophilic pneumonia.

Amyopathic dermatomyositis (ADM) is occasionally complicated by rapidly progressive interstitial pneumonia (RPIP), and in such cases, diffuse alveolar damage (DAD) is usually diagnosed at autopsy. Here, we present three patients with RPIP accompanied by ADM in whom lung disease was assessed at an early stage. High-resolution computed tomography (HRCT) carried out before the onset of dyspnoea revealed uniformly subpleural reticular opacity with faint ground-glass attenuation. At that stage, surgical lung biopsies from two patients showed histological patterns typical of cellular nonspecific interstitial pneumonia (NSIP). Despite pulse methylprednisolone and subsequent high-dose oral administration of prednisolone, lung disease progressed in all patients, with extensive areas of ground-glass opacity and consolidation observed in HRCT scans. DAD was confirmed histologically in one case. Additional administration of cyclosporine, pulse cyclophosphamide or high-dose intravenous administration of immunoglobulin rescued all patients. Our data suggest that ADM-associated interstitial pneumonia takes an aggressive course even when the radiological and histological features are consistent with NSIP. Aggressive combination therapy with high-dose steroids and immunosuppressive agents is required as early as possible for patients with this life-threatening disorder.

Our results suggest that interleukin-4 may be involved in progression of interstitial fibrosis in idiopathic pulmonary fibrosis, in which we confirmed a significant contribution of eosinophils and mast cells to interleukin-4 production.

IP-10 is mainly produced at the lung and TARC in the peripheral circulation in sarcoidosis patients. Both IP-10 and TARC cooperatively play a role in the pathogenesis of sarcoidosis.