Investigation of IL-18 and IL-12 in induced sputum of patients with IPF before and after treatment with interferon gamma-1b.
OBJECTIVE
Interleukin-18 (IL-18) has been identified as an interferon-gamma (IFN-gamma) mediator, promoting a T helper 1 (Th1) response. Th1 response is characterized by increased expression of IFN-gamma, interleukin-12 (IL-12) and interleukin-18 (IL-18). The present study aims to evaluate the role of Th1 cytokines by monitoring changes in Induced Sputum (IS) samples, before and after treatment with IFN-gamma-1b in patients with IPF.


METHODS
Fifteen patients with histologically confirmed IPF/UIP (12 male, 3 female) of median age 65 yr were prospectively studied. Ten healthy subjects (5 female, 5 male) of median age 61 yr served as control group. Patients were assigned to receive IFN-gamma-1b 200 microg (15 patients) subcutaneously three times per week for 12 months. Induced sputum (IS) IL-12 and IL-18 levels were measured before and after IFN-gamma-1b treatment in IPF patients as well as in healthy controls, using ELISA immunoassay.


RESULTS
The IL-18 levels were significantly higher in IPF samples before treatment than in healthy controls (57.05 +/- 6.9 pg/ml vs. 41.07 +/- 8.16 pg/ml, p < 0.05). A statistically significant decrease was detected in the IL-18 levels after IFN-gamma-1b treatment (57.05 +/- 6.9 vs. 42.8 +/- 5.1 pg/ml, p = 0.04). The IL-12 supernatant levels measured before and after IFN-gamma-1b treatment were not significantly different.


CONCLUSIONS
Our results may illustrate the potential role of IL-18 as an inflammatory molecule in the pathogenesis of IPF. Moreover, decrease of IL-18 levels in IPF patients, after 12 months of therapy could possibly be explained as IL-18 downregulation after IFN-gamma-1b treatment. Extended studies are needed to determine the precise role of IL-12 and IL-18 during IPF.
Antoniou
Katerina M
KM
Interstitial Lung Disease Unit, Department of Thoracic Medicine, University General Hospital, Medical School, University of Crete, Heraklion.
Tzortzaki
Eleni G
EG
Alexandrakis
Michael G
MG
Zervou
Maria
M
Tzanakis
Nikolaos
N
Sfiridaki
Katerina
K
Bouros
Demosthenes E
DE
Siafakas
Nikolaos M
NM
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000032:analysis*; D020382:Interleukin-18 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D011994:Recombinant Proteins; D012016:Reference Values; D012129:Respiratory Function Tests; D013183:Sputum / Q000276:immunology*
D000998:Antiviral Agents; D020382:Interleukin-18; D011994:Recombinant Proteins; D002245:Carbon Dioxide; D018664:Interleukin-12; D007371:Interferon-gamma; D010100:Oxygen