In vitro Cytokine Synthesis by Lymphocytes in Children in Juvenile Idiopathic Arthritis Remission Against the Background of Genetically Engineered Biologic Drug Therapy

The aim of the investigation to assess the capacity of lymphocytes for spontaneous and stimulated cytokine production in vitro in children in remission with juvenile rheumatoid arthritis treated with genetically engineered biological agents combined with immunosuppressants.

Materials and Methods. We examined 18 children (8 girls and 10 boys) aging from 2 to 12 years with various types of juvenile idiopathic arthritis treated with genetically engineered biological agents combined with immunosuppressants, no glucocorticoids were administered. The mean duration of genetically engineered biological agent therapy was 3.8 years. When included in the study all patients were recorded to have the disease remission according to Wallace criteria. Twelve age-matched children without chronic diseases and medical therapy were included in the control group. We assessed spontaneous and phytohemagglutinin (PHA)-induced cytokine synthesis (IL-2, IL-4, IL-6, IL-8, IL-10, G-CSF, IFN-γ, TNF-α), as well as their synthesis stimulation index. Cytokine concentration was determined in whole blood cultures using multiplex test systems (Bio-Plex Pro Human Cytokine) for Bio-Plex 200 (Bio-Plex Manager, version 5.0) (Bio-Rad, USA).

Results. We compared the activity of spontaneous and stimulated cytokine synthesis in children with juvenile idiopathic arthritis and controls to find a significant decrease in the spontaneous synthesis of IL-4, IL-6, IL-8, G-CSF, IFN-γ, TNF-α, and no significant differences in spontaneous production of IL-2 and IL-10. The analysis of PHA-stimulated cultures in children with arthritis showed the higher production of IL-2, IL-4, IL-6, the decreased IL-10 production, and no significant differences in the production of IL-8, G-CSF, IFN-γ, TNF-α. The calculated stimulation indices of G-CSF, IL-8, and TNF-α were similar in both groups of children, while those of IL-2, IL-4, IL-6, IFN-γ appeared to be significantly higher, and the indices for IL-10 were reduced.

Conclusion. No significant differences in stimulated synthesis levels of IL-8, G-CSF, IFN-γ, TNF-α in patients with juvenile idiopathic arthritis and in controls, and the increased stimulated IL-2, IL-4, IL-6 synthesis in children with arthritis suggest the preserved reactivity during a long-term therapy with genetically engineered biological agents in children with juvenile idiopathic arthritis.

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Zakirov R.S., Akulova S.S., Filyanskaya E.G., Semikina E.L., Mayanskiy N.A. In vitro Cytokine Synthesis by Lymphocytes in Children in Juvenile Idiopathic Arthritis Remission Against the Background of Genetically Engineered Biologic Drug Therapy. Sovremennye tehnologii v medicine 2016; 8(2): 46, https://doi.org/10.17691/stm2016.8.2.06