The effect of inf- on phagocytic cells in chronic granulamatous disease

The Effect of INF-? on phagocytic cells in Chronic Granulamatous DiseaseChronic granulomatous disease (CGD) is an inherited disorder that is caused by defects in the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme complex responsible for the generation of superoxide. CGD is characterized by recurrent life-threatening infections caused by catalase-positive bacteria and fungi and exuberant granuloma formation.Interferon gamma(INF- ?) a cytokine with diverse roles in the innate and adaptive responses. Evidence that recombinant INF- ? can enhance phagocytic oxidative metobolism led to its evaluation for use in the treatment of CGD. Despite several decades of work on INF- ? and demonstrated clinical benefits in majority of patients with CGD, it is not known yet whether to use as a prophylaxis in CGD or not.İf we compare the published and current studies on the use of INF- ? in patients with CGD, it is routinely administered prophylactically with the anti-microbial therapy or adjusted to it in the case of the severe and recurrent infections.Fifty-seven patients with CGD and twenty-one controls were enrolled to our study to assess the effects of INF- ? on phagocytic cells in CGD in a multi-center study. The effect of INF- ? on phagocyte respiratory-burst activity was determined by measuring superoxide generation using DHR-123 with calculating stimulation index (SI).A detailed individual questionnaire to be complied on enrolment includes patient?s personal date, family history, state of diagnosis, medications, clinical manifestations up to enrolment before and after INF- ? therapy. Correlation between clinical, genetic and laboratory data of CGH patients were examined.Although the effect of INF- ? on neutrophis in CGD patients by measuring SI was easily seen after one hour later and was still existing up to 24 hours, it was not occured on monocytes. When we compare the effect of the INF- ? in the CGD subgroup?s phagocytic cells by using SI, at the starting point, one hour and 24 hour later, we have seen that effect is significantly at an hour and 24.hour in the subgroups 91phox and 67 phox.The patients receiving INF-gamma therapy tend to have lesser infectious complications like severe infections, pneumonia, soft tissue infections and lymphadenitis. Aspergillus infection, tissue abcesses and granulamatous complications were also lesser in this group.The infectious complications were also lesser in 91 phox with receiving INF-gamma therapy. In the logistic regression models, it is mentioned that to be a 91 phox group was the only univarete paremeter to start INF-gamma therapy.In the summary, our study is the first clinical trial that investigate the clinical, demographic and genetic data of the CGD patients in a multi-center study in our country. Although the effect of INF-gamma therapy in CGD will be discussed in later clinica trials, we showed that in some majority of CGD patients especially 91 phox subgroup, has clinical benefit and improvement in phagocyte function.In this respects, clinicians should be analyze the in-vitro INF-gamma effect of CGD patients before starting such an expensive therapy and should start or continue it in the case of infectious or other complications.Key words: Chronic granulamatous disease, Interferon gamma, DHR-123, Stimulation index, infectious complications