DETERMINATION OF VARIOUS CYTOKINES AND TYPE III PROCOLLAGEN AMINOPEPTIDE LEVELS IN BRONCHOALVEOLARAVAGE FLUID OF THE PATIENTS WITH PULMONARY FIBROSIS: INVERSE CORRELATION BETWEEN TYPE III PROCOLLAGEN AMINOPEPTIDE AND INTERFERON-γ IN PROGRESSIVE PATIENTS

Abstract

We measured levels of cytokines and type III procollagen aminopeptides (procollagen III peptides) in bronchoalveolar lavage fluid obtained from 20 patients with stable pulmonary fibrosis (PF) and seven patients with progressive PF, and nine control subjects to determine the role of cytokines in the development of PF. Procollagen III peptide levels were markedly increased in progressive PF patients. Tumour necrosis factor-alpha, interleukin-6, transforming growth factor-beta and interferon-gamma (IFN-gamma) levels were elevated in both PF patients as compared with controls, with a tendency of higher levels in progressive patients, whereas interleukin-1 beta (IL-1 beta) level was decreased in both PF patients. When the correlation between procollagen III peptide and various cytokine levels was analysed the only significant correlation was inversely between procollagen III peptide and IFN-gamma in progressive PF patients. These results indicated that although multiple cytokines may be involved in the development of PF, the negative role of IFN-gamma in active collagen synthesis could be also important.

The Role of the Th2 CC Chemokine Ligand CCL17 in Pulmonary Fibrosis

“…This pattern of cytokine expression may be related to the potential role for the humoral response in the pathogenesis of IPF, or may be related to the inability of IFN-␥ to tilt the balance away from Th2-dependent profibrotic environment. In further support of an imbalance of the presence of Th2 cytokines, as compared with IFN-␥, is the finding that IFN-␥ levels are inversely related to the levels of type III procollagen in the BAL fluid of IPF patients (32).…”

A Placebo-Controlled Trial of Interferon Gamma-1b in Patients with Idiopathic Pulmonary Fibrosis

“…[11][12][13] In idiopathic pulmonary fibrosis, inflammation and widespread fibrosis are believed to result from repeated occult episodes of focal parenchymal injury. The condition is also characterized by an excess of profibrotic cytokines [14][15][16][17] and a relative deficiency of interferon-g . 18,19 Exogenous interferon gamma therapy inhibits the expression of these profibrotic cytokines, 20 enhances the activation of macrophages and killing of ingested bacteria, 21 shifts the T-cell response toward a macrophage-dominated inflammatory response, [22][23][24] and up-regulates the in vitro expression of antimicrobial peptides by alveolar macrophages and monocytes.…”

The Role of Transforming Growth Factor β in Lung Development and Disease

“…Patients with pulmonary fibrosis had higher TGF␤ levels if a progressive form of the disease was present. 72 In preterm neonates, increased levels of TGF␤ have been found in the BAL fluid of those patients in whom chronic lung disease of prematurity developed. 50,51 While the early phase of tissue injury in children in whom chronic lung disease subsequently develops is characterized by intense inflam- matory reactions, 73 the intensity of TGF␤ expression appears to play an important role in long-term outcome by determining the intensity of tissue remodeling and repair.…”