1,25(OH)D3 inhibits CD30+ cells in type 1 diabetes patients and increases IL-6 production in CD30- cells

Introduction: Chronic inflammation (CI) has an impact in clinical manifestation of type 1 diabetes (T1D). Important cytokines are Interleukin-6 (IL-6), IL-1β and tumor necrosis factor α. Especially IL-6 plays a key role in progress from acute to CI. To date, several studies claim that vitamin D reduces CI. We investigated if vitamin D can repress the expression of IL-6 by reducing CD30⁺T-helper cells.

Methods: Peripheral blood mononuclear cells were isolated by ficoll gradient centrifugation from T1D (n = 9) and healthy controls (HC;n = 11). T-helper cells were purified by negative selection using magnetic beads and cultivated with phytohemagglutinin alone or in combination with calcitriol (1,25(OH)₂D₃) for 3 days. The T-cell subpopulations (sp) CD3⁺CD4⁺CD25⁺CD30⁺(CD30⁺) and CD3⁺CD4⁺CD25⁺CD30^-(CD30^-) were characterized using flow cytometry. IL-6 expression and 18sRNA was measured by real time PCR and CT-values were defined as 2^{-[CT target -CT 18sRNA]}.

Results: Cells incubated with 1,25(OH)₂D₃ showed, in contrast to cells incubated without 1,25(OH)₂D₃, a decrease of CD30⁺cells (HC 6.6% vs. 1.35%; T1D 5.12% vs. 0.89% p_corrected(pc)= 0.01, respectably) and an increase of CD30^- cells (HC 92.14% vs. 97.84% pc = 1.7 × 10^-3; T1D 89.84% vs. 96.96% pc_trend = 0.08) as well as of the IL-6 expression (HC 5.82% vs. 20.27% pc = 0.17; T1D 7.27% vs.37.05% pc_trend= 0.08).

Conclusion: 1,25(OH)₂D₃ inhibits the CD30⁺T-helper cells in HC as well as in T1D. More decrease was shown in T1D which were possibly more stimulated than the cells of HC by reason of CI. It seems that 1,25(OH)₂D₃ increases the CD30^- cells. Probably because of the lower ground- stimulation of cells from the HC, there was more increase in HC than in T1D. The IL-6 expression seems to be increased under 1,25(OH)₂D₃ in HC and also in T1D. Therefore 1,25(OH)₂D₃ represses not the CI by repressing IL-6 expression. Maybe 1,25(OH)₂D₃ supports the immune system by changing the balance of CD30⁺and CD30^- cell sp.