Brand Jörg-Matthias, Frohn Christoph, Cziupka Katharina, Brockmann Christian, Kirchner Holger, Luhm Jürgen
Institute of Immunology and Transfusion Medicine, University of Lübeck, Germany.
Eur Cytokine Netw. 2004 Apr-Jun;15(2):99-104.
The peptide hormone prolactin (PRL) is produced by specialized cells in the anterior pituitary gland and in a number of sites outside the pituitary. Its biological actions consist of various roles in reproduction, lactation, and of a number of homeostatic biological activities that also include immune functions. Elevated serum PRL concentrations often correlate with abnormalities in immune responses. To determine the influence of PRL on human immune cells, human whole blood cultures were stimulated with lipopolysaccharide (LPS), supplemented with various concentrations of human recombinant PRL. We found that PRL, at concentrations achievable during pregnancy, anesthesia and medication, significantly amplified interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) synthesis in LPS-stimulated cultures, in a dose-dependent manner. Conversely, synthesis of the anti-inflammatory cytokine IL-10 only increased significantly at very high concentrations of supplemented PRL. PRL alone was not able to induce any measurable secretion of TNF-alpha, IL-10, or IL-12 in non-stimulated, whole blood cultures. However, we demonstrated that PRL, by itself or in combination with LPS, causes an increase in the binding activity of the transcription factors nuclear factor-kappaB (NFkappaB) and interferon regulatory factor-1 (IRF-1), which are known to promote TNF-alpha and IL-12 secretion. These data suggest that PRL promotes pro-inflammatory immune responses via NFkappaB and IRF-1, which may affect pathophysiological processes in physiological hyperprolactinemic states.
肽类激素催乳素（PRL）由腺垂体中的特殊细胞以及垂体外的多个部位产生。其生物学作用包括在生殖、泌乳过程中发挥多种作用，以及参与一些稳态生物学活动，其中也包括免疫功能。血清PRL浓度升高常与免疫反应异常相关。为了确定PRL对人免疫细胞的影响，用脂多糖（LPS）刺激人全血培养物，并添加不同浓度的人重组PRL。我们发现，在妊娠、麻醉和用药期间可达到的浓度下，PRL能以剂量依赖的方式显著增强LPS刺激培养物中白细胞介素（IL）-12和肿瘤坏死因子-α（TNF-α）的合成。相反，仅在添加的PRL浓度非常高时，抗炎细胞因子IL-10的合成才会显著增加。单独的PRL在未刺激的全血培养物中不能诱导任何可测量的TNF-α、IL-10或IL-12分泌。然而，我们证明，PRL单独或与LPS联合使用时，会导致转录因子核因子-κB（NFκB）和干扰素调节因子-1（IRF-1）的结合活性增加，已知这两种因子可促进TNF-α和IL-12的分泌。这些数据表明，PRL通过NFκB和IRF-1促进促炎免疫反应，这可能会影响生理性高催乳素血症状态下的病理生理过程。
