Increased Levels of Serum Interferon-gamma in Pulmonary Sarcoidosis and Relationship with Response to Corticosteroid Therapy

Abstract

The aim of this study was to evaluate serum levels of the lymphokine interferon-gamma (IFNg) in patients with chronic pulmonary sarcoidosis, and to investigate its value as a predictive marker of clinical response to corticosteroid therapy. Twenty-five patients and 28 age-matched control subjects were studied. All the patients had parenchymal shadows (Stage II or Stage III) and none had clinical evidence of extrathoracic disease. Before therapy, serum IFNg levels were significantly higher in the patient group (p less than 0.001), and 20 (80%) had values above the normal range. After oral treatment with corticosteroids for a median 13 months (range, 3 to 49 months) the levels decreased significantly (p less than 0.01). However, the falls were less pronounced in patients who had a better outcome in terms of achieving complete radiographic resolution and in those who improved in forced vital capacity by greater than or equal to 10%. The prognostic value of the pretreatment serum IFNg was explored, and a significant relationship was found between higher pretreatment levels and lower grades or radiographic abnormality assessed 3 yr after commencement of treatment (p less than 0.01). In addition, the patients who had cleared completely while receiving steroids and remained in remission had significantly higher pretreatment serum IFNg levels than did those with incomplete resolution of parenchymal shadows or radiographic relapses (p less than 0.05). We conclude that elevated levels of circulating IFNg are detectable in most untreated patients with Stage II/III pulmonary sarcoidosis and that patients with the highest levels appear to have a better chance of achieving complete resolution with corticosteroid therapy.

Pulmonary sarcoidosis: patterns of cytokine release in vitro

“…However, other clinical variables that were not assessed in this study, such as disease progression or response to therapy, may well be related to cytokine production [10,42]. Given the high variability in the clinical course of sarcoidosis, the number of patients investigated here is small, and no firm conclusions can be drawn in this respect.…”

“…We have speculated [10,11] that lymphokines, such as interferon-γ (IFN-γ) could be primarily involved. Indeed, lung lymphocytes from sarcoid patients produce excessive amounts of IFN-γ [12,13] and also IL-2 [14].…”

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis

“…Prior & Haslam [32] showed elevated IFN-concentrations in sera of patients with pulmonary sarcoidosis. Cellular expression of ICAM-1 was found immunohistochemically on epithelioid cells and giant cells in sarcoid granulomas obtained from lymph node biopsy specimens [33].…”

Presence of mRNA for interferon-gamma (IFN-γ) in blood mononuclear cells is associated with an active stage I sarcoidosis

“…Therefore, Lofgren syndrome cases represent a subset of patients with a high IFN-7-produeing potential probably having a high proportion of cells of Thl characteristic [14]. This ability seems to have a predictive power [2].…”