Background Rheumatoid arthritis (RA) is a prevalent chronic autoimmune inflammatory disease. Its pathogenesis is closely associated with a failure of endogenous immune tolerance that caused by the imbalance of pro-inflammatory T helper 17 (Th17) cells and anti-inflammatory regulatory T (Treg) cells. Low-dose Interleukin-2 (IL-2) has been showed to induce both Th17 and Treg cells' expansion and activation while IL-6 antagonist Tocilizumab suppresses the differentiation of Th17, which is expected to control the development of RA.
Objectives To study the influence of the combination of IL-2 and Tocilizumab on T cells subgroups and its clinical efficacy and safety on refractory RA.
Methods Total 50 RA patients with low Treg cells, who had been treated with glucocorticoids and DMARDs for over 6 months, were divided into three groups randomly. Patients in non-IL-2 group (n=15) were still given conventional glucocorticoids and DMARDs. Patients in IL-2 group (n=26) were not only given those treatments, but injected subcutaneously human IL-2 (aldesleukin) at 50 WIU per day for a 5 day course. Patients in IL-2 and Tocilizumab group (n=9) were not only received the treatment like IL-2 group, but also treated with Tocilizumab at the dosage of 160mg during the day 1 and day 3. The demographic features, clinical manifestations and laboratory indicators were compared before and after the treatment.
Results There was no difference among all groups in gender, age and course of the disease (p >0.05). The ratios of Th1/Th2 and Th17/Treg were significant correlated with ESR, the number of tender or swollen joints and DAS28-ESR (p<0.05) in all three groups of patients. After treatment, the number of Th17 cells and Treg cells was significantly increased in IL-2 group (p<0.01). In IL-2/Tocilizumab group after the treatment, the number of Treg cells were also significantly increased (p<0.05), but not the Th17 cells (p>0.05), leading to a quickly decrease in their ratio (p<0.05). Before the treatment, there was no difference in clinical manifestations among all three groups (p>0.05), but compared with non-IL-2 group, there was a significantly decrease in the number of tender joints (p<0.01) or swollen joints (p<0.05) and DAS28-ESR (p<0.01) in IL-2 group and IL-2/Tocilizumab group after the treatment. Patients in IL-2/ Tocilizumab group had better clinical manifestations' remission although no significant difference compared with IL-2 group (p>0.05). There was no difference in blood routine, liver and renal functions both before and after the treatment among all groups (p>0.05).
Conclusions IL-2 can effectively increase the level of Treg cells as well as that of Th17 to some degree; while IL-2 combined with Tocilizumab only effectively expand Treg cell number without Th17 increasing, thereby quickly recovers the balance of Th17 and Treg cells. This combination selectively stimulate Treg Cells leading to induce autoimmune tolerance, and seems to help RA patients achieve remission in a rapid way without over-treatment and evaluated side effect, though the long term benefits of this therapy are required to further study in more patients.
Acknowledgements The authors thank Chong Gao for the assistance.
Disclosure of Interest None declared
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