Endogenous blood maximal interferon-gamma production may predict response to interferon-gamma 1beta treatment in patients with idiopathic pulmonary fibrosis.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is an untreatable lung disorder with a mean survival of 3 years after diagnosis. Treatment with interferon-gamma (IFN-gamma) 1beta has been reported to significantly improve lung function and arterial oxygen saturation in a first randomized controlled trial; unexpectedly, these findings have not been confirmed in a subsequent large placebo-controlled randomized study. Another larger placebo-controlled randomized trial has been stopped because data analyzed at interim analysis excluded the possibility that treatment with IFN-gamma 1beta would cause a significant reduction in the risk of death.


METHODS
Seven Italian male patients diagnosed with IPF were treated with IFN-gamma 1beta (200 microg/die subcutaneously three times a week), accordingly to the indications of the Italian Drug Agency. Based on available studies the response to treatment was pre-defined as changes in either lung function (FVC and DLCO) or oxygen arterial saturation. All patients consented to provide a peripheral blood sample for endogenous IFN-gamma production measurement with the ELISpot assay before treatment and 6 months thereafter.


RESULTS
Four of 7 patients improved or stabilized their lung function after 6 months treatment. Using the ELISpot assay to quantify the maximal production of endogenous IFN-gamma on peripheral blood samples, these 4 patients had a significantly higher endogenous IFN-gamma production before therapy, as compared to the 3 patients who deteriorated (91.3 +/- 49.6 vs. 277.8 +/- 34.2 spot forming cells, p = 0.023). No significant differences were observed after 6 months of treatment.


CONCLUSIONS
These preliminary results suggest that some IPF patients might benefit from treatment with IFN-gamma 1beta and may help to interpret the results of large randomized trials, suggesting that individual susceptibility could determine clinical response to treatment.
Luppi
F
F
Center for Rare Lung Disease, University of Modena and Reggio Emilia, Italy. fabrizio.luppi@unimore.it
Losi
M
M
D'Amico
R
R
Fabbri
L M
LM
Richeldi
L
L
D000368:Aged; D015415:Biomarkers / Q000097:blood; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D007558:Italy; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012129:Respiratory Function Tests; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D011994:Recombinant Proteins; D007371:Interferon-gamma; D010100:Oxygen