Oxidative Status and Its Contribution to Extracellular Cytokine Secretion in Children with Acute Lymphoblastic Leukemia.

Recent data suggest that oxidative-antioxidative imbalance may influence cytokine secretion in children with acute lymphoblastic leukemia (ALL). Plasma cytokines concentrations are reported to have an effect on clinical course of the patients with lymphoid malignancies. The aim of the study was analysis of oxidative status (Malonylodialdehyde, MDA) and antioxidant defense (Superoxide dismutase, SOD; glutathione peroxidase, GPX; total antioxidant status, TAS and vitamin E) in peripheral blood and evaluation of plasma concentration of IL-2, IL-4, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia.

Material and methods: Study group consisted of 23 newly diagnosed ALL children, including 13 boys and 10 girls, with median age 5 years (range, 0.5–16). Control group consisted of 21 healthy children (11 boys and 7 girls) with median age 7 years (range, 2–17). TAS, SOD, GPX status were estimated using commercially available Randox Laboratories Ltd kits. Vitamin E and MDA plasma concentrations were measured spectrofluorimetrically. Cytokine concentrations were measured by quantitative immunoassay tests: IL-2 and IL-4 plasma levels were assessed using Bender MedSystems test (Vienna, Austria), IL-10 and TNF-alpha by R&D system tests. All assays were performed twice: on diagnosis and 6 weeks thereafter.

Results: GPX activity in study group was significantly higher before and during treatment than in control subjects (1.5-fold, p=0.02 and 2-fold, p=0.0007, respectively). MDA concentrations were higher in ALL group before treatment (1.4-fold, p=0.0001) and 6 weeks thereafter (1.2 fold, p=0.01) than in control group. SOD activity, TAS and vitamin E concentrations did not differ between the groups. IL-10 level was found to be significantly increased on ALL diagnosis, but not during therapy, when compared to control group (2-fold, p=0.02). TNF-alpha level was higher in patients before treatment then during treatment (3-fold, p=0.02) and as compare to the controls (2,5-fold, ns). IL-2 and IL-4 plasma concentrations were comparable in all groups in both time points. There was a correlation in children with ALL after 6 weeks therapy between MDA and IL-10 concentrations (r=0.59, p<0,05) as well as MDA and TNF-alpha concentrations (r=0,58, p<0,05). In control group MDA was correlated with IL-10(r=0.59, p<0.05). Median follow-up of the study group is 23 months, and at that time relapses occurred in 3 out of 23 patients. 2-fold decrease in median GPX were observed in patients, who relapsed afterward,. Median IL-10 plasma concentrations in children, who subsequently relapsed were 4-fold higher at diagnosis and 8-fold higher after 6 weeks of therapy then in patients who are still in remission (despite of achieving complete remission by all study group at 6th week of treatment).

Conclusions: Oxidation process in plasma of children with ALL is significantly increased on diagnosis. Pro-oxidative status may contribute to IL-10 and TNF secretion and affect efficacy of treatment.