Microglia play a role in mediating the effects of cytokines on the structure and function of the rat pineal gland

The role of the pineal gland in regulating immune function has been extensi vely investigated. However, there is little information about possible feed back mechanisms of immunological factors on pineal gland neuroendocrine fun ctions. Therefore, experiments were designed to test the effects of cytokin es (interferon-gamma, lFN-gamma; interleukin-1 beta, IL-1 beta: tumor necro sis factor alpha, TNF-alpha; transforming growth factor-beta1, TGF-beta1) o n pinealocytes and the role of pineal microglia in mediating these cytokine effects in the pineal gland of the rat. Our studies showed that IFN-gamma enhanced 5-hydroxytryptamine (5-HT) content (measured by high-performance l iquid chromatography, HPLC) and increased pinealocyte process length in pin eal cultures. IL-1 beta treatment decreased 5-HT content in both cell and o rgan culture, but exhibited no effect on pinealocyte process length. 5-HT c ontent and process length were decreased by TNF-alpha treatment. IFN-gamma and IL-1 beta exhibited no significant effect in the absence of microglia i n cell cultures. In contrast, TNF-alpha caused a further decline in 5-HT co ntent even in the absence of microglia in the cultures. The effects of TNF- alpha were probably due to toxic effects, since an increased number of pykn otic nuclei were observed in treated cultured explants. TGF-beta1 treatment caused aggregation of pinealocytes in cultures and suppressed process leng th and 5-HT content. In conclusion, cytokine effects on pinealocytes may be mediated by microglia (IFN-gamma and IL-1 beta) or act directly on pinealo cytes (TNF-alpha). The presence of IL-1 beta and TGF-beta1 protein in the p ineal gland and the suppressive effect of TGF-beta1 on pinealocytes in cult ures further suggest that endogenous cytokines play regulatory roles in res ponse to peripheral homeostatic changes.