Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subjects with juvenile rheumatoid arthritis.

BACKGROUND

To evaluate T helper 1 (Th1)/Th2 cells and cytokines in patients with three different subtypes of juvenile rheumatoid arthritis (JRA).

METHODS

Peripheral blood was obtained from 25 children with JRA suffering from active arthritis (8 systemic, 9 pauciarticular and 8 polyarticular). Eight healthy children were recruited as controls. T helper cells from peripheral blood mononuclear cells (PBMC) were evaluated by using intracellular staining analysis of cytokine production with 3-colored flow cytometry. A Th1 cell was defined as an interferon-gamma (IFN-gamma) producing CD4+ cell, and a Th2 cell as an interleukin-4 (IL-4) producing CD4+ cell. The production of IL-2, IL-4, IL-5 and IFN-gamma from PBMC was measured by ELISA.

RESULTS

In comparison with normal controls, the patients with JRA had significantly fewer Th2 cells among their PBMC (0.78 +/- 0.56% vs. 5.44 +/- 2.33%, p < 0.001). The percentage of Th1 cells among PBMC was not different between patients and normal controls (4.32 +/- 3.24% vs. 4.52 +/- 2.56%, p > 0.5). The ratio of Th1/Th2 cells in the patient group was significantly higher than the control group (8.38 +/- 8.63 vs. 0.95 +/- 0.66, p < 0.001). After 24-hour culture, the PBMC from JRA patients produced less IL-4 than that of controls (3.61 +/- 0.56 pg/mL vs. 4.29 +/- 0.68 pg/mL, p = 0.002). The production of IL-2, IL-5, and IFN-gamma did not show significant differences between JRA patients and normal controls.

CONCLUSION

Decreased IL-4 producing T-helper cells were identified in all three subtypes of JRA. This implicates that an imbalance of Th sub-populations might be a predominant factor in JRA pathogenesis.