ENDOGENOUS BLOOD MAXIMAL INTERFERON-γ PRODUCTION MAY PREDICT RESPONSE TO INTERFERON-γ 1β 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) 1 beta 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 1 beta would cause a significant reduction in the risk of death. Methods: Seven Italian male patients diagnosed with IPF were treated with IFN-gamma 1 beta (200 mu g/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. Discussion: These preliminary results suggest that some IPF patients might benefit from treatment with IFN-gamma 1 beta and may help to interpret the results of large randomized trials, suggesting that individual susceptibility could determine clinical response to treatment. (Sarcoidosis Vasc Diffuse Lung Dis 2009; 26: 64-68)