Different angiogenic CXC chemokine levels in bronchoalveolar lavage fluid after interferon gamma-1b therapy in idiopathic pulmonary fibrosis patients.
OBJECTIVE
Pulmonary fibrosis is a devastating disease with few treatment options. Angiogenesis that leads to aberrant vascular remodeling is regulated by an opposing balance of angiogenic and angiostatic factors. The present study aims to evaluate the role of three angiogenic (IL-8, ENA-78 and GRO-a) and three angiostatic (MIG, IP-10, ITAC) chemokines in bronchoalveolar lavage fluid (BALF), before and after treatment with Interferon gamma-1b (IFN gamma-1b).


METHODS
We studied prospectively 20 patients (16 males, 4 females) of median age 68 years (range, 40-75) with histologically confirmed IPF/UIP. Patients were assigned to receive IFN gamma-1b 200 microg sc thrice a week. Angiogenic and angiostatic mediators' levels were measured by ELISA kits.


RESULTS
The levels of the angiogenic chemokines significantly decreased after 12 months (mo) of IFN-gamma-1b treatment (median values in pg/ml, IL-8/CXCL8: 640 vs. 81, p<0.05, ENA-78/CXCL5: 191 vs. 51, p<0.005 and GRO-alpha: 1827 vs. 710, p<0.005). No significant differences were detected in the levels of the angiostatic chemokines after therapy (median values in pg/ml, IP-10/CXCL10: 56 vs. 56.5, p=0.6, ITAC/CXCL11: 43 vs. 47, p=0.11). However, a significant decrease in the MIG/CXCL9: 66 vs. 31, p=0.006, has been detected.


CONCLUSIONS
These findings support the notion that IFN gamma may be one of the important mediators regulating angiogenetic balance in IPF. However, IFN gamma-1b decreases MIG levels, finding that in association with no alteration in IP-10 and I-TAC levels, could explain in part the nonbeneficial effect of this drug in IPF.
Antoniou
Katerina M
KM
Department of Thoracic Medicine, University General Hospital, Medical School, University of Crete, Heraklion, 71110 Crete, Greece.
Tzanakis
Nikolaos
N
Tzortzaki
Eleni G
EG
Malagari
Katerina
K
Koutsopoulos
Anastassios V
AV
Alexandrakis
Michael
M
Wells
Athol U
AU
Siafakas
Nikolaos M
NM
D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D043168:Angiostatins / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D019743:Chemokines, CXC / Q000378:metabolism*; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
D043925:Angiogenesis Inducing Agents; D019743:Chemokines, CXC; D011994:Recombinant Proteins; D007371:Interferon-gamma; D043168:Angiostatins