Amento E P
Department of Medicine, Harvard Medical School, Boston, MA.
Steroids. 1987 Jan-Mar;49(1-3):55-72. doi: 10.1016/0039-128x(87)90079-1.
The investigation of the potential influence of 1,25-(OH)2D3 on immune cells has expanded our understanding of hormone-cytokine interactions. 1,25-(OH)2D3 stimulates phenotypic and function changes in immature monocytes, alters protein synthesis, increases adherence, and augments interleukin-1 secretion. T lymphocyte proliferation and B cell immunoglobulin production are inhibited by the hormone. 1,25-(OH)2D3 decreases IL 2 and IFN-gamma synthesis by activated T lymphocytes in association with decreases in mRNA for these proteins. The step from the investigation of in vitro interactions to an understanding of in vivo effects of 1,25-(OH)2D3 on immune cells requires further study. On the basis of information at hand, such as the potential for macrophage conversion of 25-OH-D3 to 1,25-(OH)2D3, decreased or increased macrophage function in association with vitamin D3 status in vitro and in vivo, as well as altered T cell subset ratios and proliferative responses with administration of the hormone, it is tempting to speculate that 1,25-(OH)2D3 exerts an influence on immune cell function in concert with other recognized soluble mediators of monocyte and lymphocyte origin. The primary influence of 1,25-(OH)2D3 may vary with the tissue site. Systemic levels of hormone may aid in maintaining tonic immunosuppression and thus prevent trivial antigenic stimuli from initiating an immune response. Upon initiation of an immune response to a significant antigenic challenge 1,25-(OH)2D3 may, in concert with other suppressor mechanisms, limit the extent of the host response by inhibition of IL 2 and IFN-gamma production. At local sites of chronic inflammation concentrations of 1,25-(OH)2D3 may be elevated and may act in an autocrine or paracrine fashion to alter the immune response, for example, by increasing IL 1 production and antigen presentation by tissue monocyte/macrophages. The activation of T cells is associated with the synthesis of 1,25-(OH)2D3 receptors, thus potentially limiting T cell proliferation in the presence of the hormone. Other biological actions of IL 1, however, including effects on cells in bone, joint, and brain may be augmented. Thus, the end result of the opposing effects of 1,25-(OH)2D3 on immune cells and their secretory products may vary with the specific cells involved, their state of maturation and activation, and the local concentrations of the hormone. Studies to date support the concept of an expanded role for 1,25-(OH)2D3 in immune cell biology.
对1,25 -（OH）₂D₃对免疫细胞潜在影响的研究拓展了我们对激素 - 细胞因子相互作用的理解。1,25 -（OH）₂D₃刺激未成熟单核细胞的表型和功能变化，改变蛋白质合成，增加黏附，并增强白细胞介素 - 1的分泌。该激素抑制T淋巴细胞增殖和B细胞免疫球蛋白的产生。1,25 -（OH）₂D₃与这些蛋白质的mRNA减少相关联，降低活化T淋巴细胞产生的白细胞介素 - 2和干扰素 - γ。从体外相互作用的研究到理解1,25 -（OH）₂D₃对免疫细胞的体内作用这一步骤需要进一步研究。基于现有信息，如巨噬细胞将25 - OH - D₃转化为1,25 -（OH）₂D₃的可能性、体外和体内巨噬细胞功能与维生素D₃状态相关的降低或增加，以及给予该激素后T细胞亚群比例和增殖反应的改变，很容易推测1,25 -（OH）₂D₃与其他公认的单核细胞和淋巴细胞来源的可溶性介质协同作用，对免疫细胞功能产生影响。1,25 -（OH）₂D₃的主要影响可能因组织部位而异。激素的全身水平可能有助于维持强直性免疫抑制，从而防止轻微抗原刺激引发免疫反应。在对重大抗原挑战启动免疫反应时，1,25 -（OH）₂D₃可能与其他抑制机制协同作用，通过抑制白细胞介素 - 2和干扰素 - γ的产生来限制宿主反应的程度。在慢性炎症的局部部位，1,25 -（OH）₂D₃的浓度可能升高，并可能以自分泌或旁分泌方式发挥作用，改变免疫反应，例如，通过增加组织单核细胞/巨噬细胞的白细胞介素 - 1产生和抗原呈递。T细胞的活化与1,25 -（OH）₂D₃受体的合成相关，因此在该激素存在的情况下可能潜在地限制T细胞增殖。然而，白细胞介素 - 1的其他生物学作用，包括对骨、关节和脑细胞的影响可能会增强。因此，1,25 -（OH）₂D₃对免疫细胞及其分泌产物的相反作用的最终结果可能因所涉及的特定细胞、它们的成熟和活化状态以及激素的局部浓度而异。迄今为止的研究支持1,25 -（OH）₂D₃在免疫细胞生物学中具有扩展作用的概念。
