The activation of monocyte and T cell networks in patients with bipolar disorder

Objectives

We recently described a monocyte pro-inflammatory state in patients with bipolar disorder (BD). We hypothesized that the CD4⁺T cell system is also activated and determined percentages of Th1, Th2, Th17 and CD4⁺CD25^highFoxP3⁺ regulatory T cells.

Methods

We carried out a detailed FACS analysis to determine the various T cell subsets and used frozen stored peripheral blood mononuclear cells (PBMC) of 38 BD patients (of whom we previously had tested monocytes for pro-inflammatory gene expression ( Drexhage et al., 2010a] and Padmos et al., 2008])) and of 22 age/gender matched healthy controls (HC). In addition the cytokines CCL2, IL-1β, IL-6, TNF-α, PTX3, IL-10, IFN-γ, IL-17A, IL-4, IL-5 and IL-22 were measured in serum.

Results

(a) Serum sCD25 levels and percentages of anti-inflammatory CD4⁺CD25^highFoxP3+ regulatory T cells were higher, the latter in BD patients <40 years of age. Percentages of Th1, Th2 and Th17 cells were normal.(b) Of the pro-inflammatory monocyte cytokines CCL2 and PTX3 were raised in serum.(c) The monocyte pro-inflammatory state and the raised percentages of CD4⁺CD25^highFoxP3⁺ regulatory T cells occurred independently from each other.(d) In BD patients positive for thyroid autoimmune disease a significantly reduced percentage of CD4⁺CD25^highFoxP3⁺ regulatory T cells was found as compared to BD patients without AITD.

Conclusion

Our data show an enhancement of pro-inflammatory monocyte and anti-inflammatory T cell forces in BD patients. A lack of anti-inflammatory T cell forces co-occurred with AITD in BD patients.