A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. The International Chronic Granulomatous Disease Cooperative Study Group.
IFN-gamma treatment of cultured monocytes from an IFN-gamma-responsive CGD patient increased the steady state level of RNA transcripts from the X-CGD gene from barely detectable up to approximately 5% of normal.
This study demonstrates partial correction of the cellular defects in chronic granulomatous disease by interferon gamma and provides a basis for clinical trials of the agent.
These findings demonstrate the responsiveness of one essential component of the phagocyte oxidase system to activation by interferon gamma and provide a rationale for its use to augment phagocytic function in chronic granulomatous disease.
In a recent randomized, placebo-controlled trail, short-term prophylactic use of recombinant human interferon gamma (rIFN-gamma 1b) reduced the risk of serious infection in CGD patients by 67%, The current study evaluated the safety and effectiveness of long-term rIFN-gamma therapy in CGD patients.
During the international placebo-controlled trial on the efficacy of interferon-gamma (IFN-gamma) in chronic granulomatous disease (CGD), 19 patients entered the study via our Institute.
After randomization, 9 CGD patients (4 with gp91phox, 3 with p47phox, 1 with p67phox deficiency and 1 with unspecified CGD) were given IFN-gamma, either 50 or 100 microg/m2 subcutaneously on 2 consecutive days after double blinded randomization.
Although current management, including prophylactic use of antimicrobial agents and interferon-gamma, has significantly improved its prognosis, CGD continues to be associated with significant morbidity and mortality from life-threatening infections and complications.
Interferon-gamma improves splicing efficiency of CYBB gene transcripts in an interferon-responsive variant of chronic granulomatous disease due to a splice site consensus region mutation.
Based on an increase of neutrophil superoxide-generating ability in response to interferon gamma (IFN-gamma) in a single patient with CGD, multicentered group studies demonstrated a beneficial effect of prophylactic IFN-gamma.
Because interferon-gamma is the key cytokine involved in mycobacterial immunity, there may be a stronger indication for its use in CGD patients living in areas endemic for TB.
However, patients with defective IL-12/23-interferon-gamma circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella.
Here, we show that IFNγ induces normal levels of kynurenine in cultures of O(2)(·)-deficient monocytes, dendritic cells, and polymorphonuclear leukocytes from gp91(PHOX)- or p47(PHOX)-deficient human CGD donors.
These results suggest that the in vivo use of IFN-γ may augment ROS generation in CGD neutrophils, thus leading to the successful treatment of severe IPA.
Recombinant IFN-γ administration is licensed for the prophylaxis of infection (bacterial and fungal) in patients with the phagocyte functional deficiency syndrome chronic granulomatous disease, although the benefits appear limited.
Specifically, macrophage-activating cytokines such as interferon gamma (IFNγ) and granulocyte colony-stimulating factor (GM-CSF) are commercially available immune potentiators used to prevent infections in patients with chronic granulomatous disease and febrile neutropenia, respectively.
The cytokine interferon-γ (IFN-γ) is approved as a drug to treat chronic granulomatous disease (CGD) and osteopetrosis and is also used in hyperimmunoglobulin E syndromes.
Interferon-γ (IFN-γ), currently delivered as a subcutaneous injection for chronic granulomatous disease and osteopetrosis, is a cytokine that can stimulate macrophage function and inhibit fibrotic pathways.