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Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis.
Respir Med. 2007 Aug; 101(8):1821-9.RM

Abstract

Idiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-gamma-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-beta, CTGF) and immunomodulatory/antimicrobial activity (IFN-gamma), in the lungs of patients with IPF. Fourteen (14) patients with an established diagnosis of IPF received either 200 microg of IFN-gamma-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor beta1 (TGF-beta1), connective-tissue growth factor (CTGF), and interferon-gamma (IFN-gamma) genes in lung tissue before and after treatment with IFN-gamma-1b or colchicine. Marked mRNA expression of TGF-beta1 and CTGF, but complete lack of interferon-gamma was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-gamma gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-beta1 remained almost stable before and after treatment, in the IFN-gamma-1b group, while TGF-beta1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-gamma-1b group (p=0.04). In addition, the IFN-gamma-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02). In conclusion, we report the effect of antifibrotic agents (IFN-gamma-1b and colchicine) in TGF-beta, CTGF, and endogenous IFN-gamma gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings.

Authors+Show Affiliations

Department of Thoracic Medicine, Medical School University of Crete, 71110 Heraklion, Crete, Greece.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

17391951

Citation

Tzortzaki, Eleni G., et al. "Effects of Antifibrotic Agents On TGF-beta1, CTGF and IFN-gamma Expression in Patients With Idiopathic Pulmonary Fibrosis." Respiratory Medicine, vol. 101, no. 8, 2007, pp. 1821-9.
Tzortzaki EG, Antoniou KM, Zervou MI, et al. Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis. Respir Med. 2007;101(8):1821-9.
Tzortzaki, E. G., Antoniou, K. M., Zervou, M. I., Lambiri, I., Koutsopoulos, A., Tzanakis, N., Plataki, M., Maltezakis, G., Bouros, D., & Siafakas, N. M. (2007). Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis. Respiratory Medicine, 101(8), 1821-9.
Tzortzaki EG, et al. Effects of Antifibrotic Agents On TGF-beta1, CTGF and IFN-gamma Expression in Patients With Idiopathic Pulmonary Fibrosis. Respir Med. 2007;101(8):1821-9. PubMed PMID: 17391951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis. AU - Tzortzaki,Eleni G, AU - Antoniou,Katerina M, AU - Zervou,Maria I, AU - Lambiri,Irini, AU - Koutsopoulos,Anastassios, AU - Tzanakis,Nikolaos, AU - Plataki,Maria, AU - Maltezakis,George, AU - Bouros,Demosthenes, AU - Siafakas,Nikolaos M, Y1 - 2007/03/27/ PY - 2006/09/26/received PY - 2006/12/26/revised PY - 2007/02/10/accepted PY - 2007/3/30/pubmed PY - 2007/12/6/medline PY - 2007/3/30/entrez SP - 1821 EP - 9 JF - Respiratory medicine JO - Respir Med VL - 101 IS - 8 N2 - Idiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-gamma-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-beta, CTGF) and immunomodulatory/antimicrobial activity (IFN-gamma), in the lungs of patients with IPF. Fourteen (14) patients with an established diagnosis of IPF received either 200 microg of IFN-gamma-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor beta1 (TGF-beta1), connective-tissue growth factor (CTGF), and interferon-gamma (IFN-gamma) genes in lung tissue before and after treatment with IFN-gamma-1b or colchicine. Marked mRNA expression of TGF-beta1 and CTGF, but complete lack of interferon-gamma was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-gamma gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-beta1 remained almost stable before and after treatment, in the IFN-gamma-1b group, while TGF-beta1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-gamma-1b group (p=0.04). In addition, the IFN-gamma-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02). In conclusion, we report the effect of antifibrotic agents (IFN-gamma-1b and colchicine) in TGF-beta, CTGF, and endogenous IFN-gamma gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings. SN - 0954-6111 UR - https://www.unboundmedicine.com/medline/citation/17391951/Effects_of_antifibrotic_agents_on_TGF_beta1_CTGF_and_IFN_gamma_expression_in_patients_with_idiopathic_pulmonary_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0954-6111(07)00078-9 DB - PRIME DP - Unbound Medicine ER -