Interleukin-10 Attenuates Behavioral, Immune and Neurotrophin Changes Induced by Chronic Central Administration of Interleukin-1β in Rats

Activated microglia can trigger pro-inflammatory cytokine releases and neuroinflammation, which may inhibit astrocytes to produce neurotrophins and anti-inflammatory factors. Both eventually lead to neuron apoptosis or death. Furthermore, effective antidepressant or anti-dementia treatments can reduce pro-inflammatory cytokines, while enhance interleukin (IL)-10 production. However, the underline mechanism by which IL-10 modulates glial cell function, hence improves cognitive impairment or depression-like behavior is unknown. This study evaluated whether and how IL-10 attenuated chronic IL-1β administration-induced behavioral changes and the possible involved mechanisms.

Rats received intracerebroventricular injection of IL-1β and/or IL-10 for 14 days. Then animal memory and depression-like behavior, pro-inflammatory cytokines, glial activities, expression of brain-derived neurotrophic factor (BDNF), Trk B, p75, and apoptosis-related genes were studied.

Compared to controls, significantly increased latent time and swimming distance in the Morris-water-maze, decreased sucrose consumption, and decreased locomotor and center zone entries in the open-field were found in rats administrated with IL-1β. These changes were associated with the reduction of GFAP expression, and concentrations of BDNF and anti-inflammatory cytokine IL-10, but the increase in the expressions of CD11b, TrkB, p75, and Caspase-3, the ratio of Bax/Bcl-2, and the concentrations of IL-1β, tumor necrosis factor-α, and IL-6. IL-10 treatment markedly attenuated IL-1β-induced above changes, except for the expressions of neurotrophin receptors.

IL-10-improved behavioral changes may be through suppressing microglia activity and inflammation, while restoring astrocyte function and BDNF expression.