Intracellular expression of TNF-α and IL-8 of peripheral blood monocytes and antioxidant defence in nephrotic syndrome

Abstract



Background. Minimal change nephrotic syndrome is accompanied by and probably related to an abnormal T-lymphocyte and monocyte function. Several immunological abnormalities are in favor of this hypothesis, but until now the precise nature and cause of the disease is not established.

Methods. In the present study we measured the expression of TNF-α and IL-8 in peripheral blood monocytes. In addition total antioxidant status (TAS) as well as the antioxidant enzymes activity were measured respectively, in the serum and erythrocytes. 39 children with NS were studied. Of these 20 with the first episode of NS formed group I, and 19 children in remission (>6 month) of NS formed group II. The age range was 4-17 years with a mean of 8.4. Twenty-fife healthy children matched for age constituted the control group. The intracellular expression of cytokines was detected after incubation with Brefeldin A (BFA).

Results. TAS was significantly reduced in group I compared to the controls (0.74±0.16 mmol/l vs. 1.14±0.49 mmol/l; p=0.002). Glutathione peroxidase activity was lower in group I compared to the controls (24.56±4.06 U/g Hb vs. 31.25±5.67 U/g Hb, p=0.013). Glutathione reductase activity was lower in group I than in the controls (8.30±1.97 U/g Hb vs.9.96±3.08 U/g Hb, p=0.048) and was also lower in group II than in the controls (6.98±2.89 U/g Hb vs.9.96±3.08 U/g Hb, p=0.016). There was no difference in superoxide dismutase activity between the 3 groups (Group I - 1168.45±234.45 U/g Hb; Group II - 1146.56±287.43 U/gHb; Control - 1056.23±216.32 U/gHb). Intracellular expression of
TNF-α was significantly higher in group I (63.33±24.75%) compared to the controls (28.19±29.06%, p=0.0005). In children with first episode of NS, negative correlation between GR activity and TNF-a expression was found (CD14+TNF-? + = 120.24 - 6.850 * GR; r=0.5463; p=0.012). Intracellular expression of IL-8 in group I was higher compared to both the control group (35.48±20.50% vs 16.42±15.06%; p=0.002) and to group II (35.48.±20.50% vs 14.86±10.70% p=0.007).

Conclusions. The results of the study indicate that first episode of NS in children is associated with increased TNF-α and IL-8 intracellular expression in peripheral blood monocytes. This may be partly related to defects of the antioxidant system.