Longitudinal comparison of IL-6, IL-10, and IL-12 cytokine profiles in adult and childhood-onset systemic lupus erythematosus

Abstract

Objective: To compare the levels of Th1 (IL-12) and Th2 (IL-6 and IL10) cytokines over a two-year period among systemic lupus erythematosus patients with childhood-onset (cSLE), adult-onset (sSLE), and healthy controls, and correlate with their clinical, laboratory, and treatment manifestations.

Methods: The study included 63 patients with cSLE [57 (90%) women; mean age 19.7 ± 4.3 years (range = 10-29); mean disease duration 7.3 ± 4.2 years (range 2-15)], 67 patients with aSLE [65 (97%) women; mean age of 39.9 ± 11.8 years (range 21-68); disease duration 7.7 ± 3.1 years (range 4-16)], and 40 healthy controls [36 (90%) women; mean age of 29.6 ± 10 years (range 12-49)]. cSLE and aSLE patients were paired by disease duration. Clinical and laboratory manifestations, disease activity (SLEDAI), cumulative damage (SDI), and current drug exposures were evaluated. Symptoms of anxiety and depression were evaluated by the Beck inventory (BAI and BDI, respectively). Th1 (IL-12) and Th2 (IL-6 and IL-10) cytokines were measured by the ELISA test. Data were collected at four different time points (TI, TII, TIII, and TIV) and compared by non-parametric tests.

Results: IL-6 levels were significantly higher in aSLE patients compared to healthy controls at times I, II, and III (TI p = 0.013, TII p = 0.015, TIII p = 0.004, and TIV p = 0.634). However, no difference was observed between cSLE patients and healthy controls (TI p = 0.223, TII p = 0.613, TIII p = 0.341, and TIV p = 0.977). In addition, no difference was observed between aSLE and cSLE patients (TI p = 0.377, TII p = 0.123, TIII p = 0.105, and TIV p = 0.591). The levels of IL-12 were significantly higher in cSLE patients compared to healthy controls at all time points (TI p = 0.04, TII p < 0.001, TIII p = 0.015, and TIV p = 0.021). aSLE patients showed significantly elevated levels when compared to healthy controls at time III and IV (TI p = 0.752, TII p = 0.827, TIII p = 0.011*, and TIV p < 0.001*). cSLE patients showed significantly higher levels than aSLE patients at times I and II (TI p = 0.07*, TII p < 0.001*, TIII p = 0.998, and TIV p = 0.140). In aSLE patients, IL-6 was associated with headache (p = 0.006), arthritis (p = 0.044), and nephritis (p = 0.012); IL-10 was associated with nephritis (p = 0.043), hypocomplementemia (p = 0.001), and disease activity (p = 0.001); in these patients, IL-12 was associated with alopecia (p = 0.025) and leukopenia (p = 0.044). In cSLE patients, IL-6 was associated with arthritis (p = 0.022) and malar rash (p = 0.012).

Conclusion: aSLE and cSLE patients with long disease duration present similar levels of cytokines, despite differences in clinical activity patterns over time.

Fig. 1

Comparison of levels of IL-6 between cSLE, aSLE, and controls at the four time points evaluated. *p ≤ 0.05 is considered statistically significant.

Fig. 2

Comparison of levels of IL-10 between cSLE, aSLE, and controls in the four time points evaluated. *p ≤ 0.05 is considered statistically significant.

Fig. 3

Comparison of levels of IL-12 between cSLE, aSLE, and controls in the four time points evaluated. *p ≤ 0.05 is considered statistically significant.