The role of the pineal gland in regulating immune function has been extensively investigated. However, there is little information about possible feedback mechanisms of immunological factors on pineal gland neuroendocrine functions. Therefore, experiments were designed to test the effects of cytokines (interferon-gamma, IFN-γ; interleukin-1β, IL-1β; tumor necrosis factor-alpha, TNF-α; transforming growth factor-β1, TGF-β1) on pinealocytes and the role of pineal microglia in mediating these cytokine effects in the pineal gland of the rat. Our studies showed that IFN-γ enhanced 5-hydroxytryptamine (5-HT) content (measured by high-performance liquid chromatography, HPLC) and increased pinealocyte process length in pineal cultures. IL-1β treatment decreased 5-HT content in both cell and organ culture, but exhibited no effect on pinealocyte process length. 5-HT content and process length were decreased by TNF-α treatment. IFN-γ and IL-1β exhibited no significant effect in the absence of microglia in cell cultures. In contrast, TNF-α caused a further decline in 5-HT content even in the absence of microglia in the cultures. The effects of TNF-α were probably due to toxic effects, since an increased number of pyknotic nuclei were observed in treated cultured explants. TGF-β1 treatment caused aggregation of pinealocytes in cultures and suppressed process length and 5-HT content. In conclusion, cytokine effects on pinealocytes may be mediated by microglia (IFN-γ and IL-1β) or act directly on pinealocytes (TNF-α). The presence of IL-1β and TGF-β1 protein in the pineal gland and the suppressive effect of TGF-β1 on pinealocytes in cultures further suggest that endogenous cytokines play regulatory roles in response to peripheral homeostatic changes.
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Tsai, S., O'Brien, T. & McNulty, J. Microglia play a role in mediating the effects of cytokines on the structure and function of the rat pineal gland. Cell Tissue Res 303, 423–431 (2001). https://doi.org/10.1007/s004410000330
- IFN-γ IL-1β TGF-β1, TNF-α Pinealocyte Rat (Sprague Dawley)