Background:In patients with rheumatoid arthritis (RA), a high prevalence of depression and anxiety is observed, and the severity of these conditions depends on the degree of vitamin D deficiency. The role of the main mediator, with the help of which psychological and physical stress factors can contribute to the development of depression and systemic diseases, has been attributed to inflammation in recent years.Objectives:to assess the dependence of depressive disorders on vitamin D deficiency and the level of pro-inflammatory cytokines in patients with RA.Methods:88 women with a reliable diagnosis of RA (mean age 54.2 ± 12.0 years old, disease duration 9.0 [3.5; 16.0] years) were under observation. Beck’s depression inventory (BDI-II) was used to assess the presence of depressive symptoms. ELISA test was used to measure serum cytokines (IL-1, IL-6) and serum 25(OH)D levels.Results:The presence of depression was found in 66% of patients with RA. An insufficient level of 25(OH)D (<30 ng / ml) was determined in 89.8% of cases. In RA patients with no signs of depression, the level of 25(OH)D showed maximum values and significantly differed from that in the groups of patients with moderate (p = 0.028) and severe depression (p <0.001). A negative correlation (r = -0.38, n = 88, p <0.05) was established between the level of 25(OH)D and the severity of depression. A positive relationship was also found between 25(OH)D and ESR (r = 0.29, n = 73, p <0.05) and a negative relationship with the number of painful joints (r = -0.29, n = 76, p <0.05). Probably, vitamin D is indirectly involved in inflammatory processes in joints and in central sensitization, which provokes chronic pain and psychological disorders in patients with RA.The level of IL-6 in patients with RA with moderate and severe depression (n=18; 14.6 ± 6.7 pg/ml) significantly exceeded the parameters of patients with RA without depressive disorders (n=30; 9.8 ± 3.7; p = 0.003). There was also a tendency to increase IL-6 in the group of patients with moderate and severe depression compared with patients with mild depression (p = 0.06). IL-1β values significantly increased with the progression of depression (without depression – mild depression, p = 0.034; mild – moderate, p <0.001; moderate – severe depression, p = 0.044). A positive correlation of average severity was revealed between the degree of depression (according to BDI-II) and the dose of glucocorticoids (GC) at the time of the study (r = 0.33, p = 0.002). An increase in the GC dose in the short term can aggravate depressive disorders in RA patients (Table 1).Table 1.Indicators of levels of depression and IL-1β depending on the dose of GCGroup I (n=26), without GCGroup II (n=45),GC <10 mg / dayGroup III (n=17),GC ≥10 mg / dayDepression level according to BDI-II, points (Me [P25; P75])8,5[5;16]14[9;17]19[14;29] *III-IIL-1β level, pg / ml (M ± SD)4,57 ± 1,83*I-II6,04 ± 3,276,52 ± 5,16* - intergroup differences are reliable, p <0.05Patients who used GC in a daily dose of ≥10 mg / day (group III) had a higher degree of depression compared to patients with RA from group I (z = -2.98; p = 0.003). In patients with RA in the first group, the level of IL-1β was significantly higher (pI-II = 0.039) than in patients with GC prescription in minimal doses (up to 10 mg / day) (Table 1). Glucocorticoid hormones suppress pro-inflammatory cytokines. As a rule, this effect is not observed in patients with depression. This fact may indicate a violation of homeostatic mechanisms. IL-1β is thought to be the first step in the pro-inflammatory response to psychological stress and is capable of inducing a subsequent cascade of other inflammatory cytokine responses.Conclusion:Restoring the normal level of 25(OH)D in the blood serum of patients with RA can positively affect psychological indicators by reducing the severity of depression and manifestations of pain. The activation of pro-inflammatory cytokines during stress and depression suggests that suppression of the inflammatory response can also reduce the symptoms of depression in RA patients.Disclosure of Interests:None declared
Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation