The interleukin 12 (IL-12) family comprises a group of heterodimeric cytokines that can cope with a great variety of immune conditions as the microenvironment demands. By sharing cytokine and receptor subunits, IL-12 (comprised of p40/p35 subunits), IL-23 (p40/p19), IL-27 (p28/EBI3), and IL-35 (p35/EBI3) represent, as a whole, a highly versatile system participating in controlling the continuum from inflammation to tolerance. Promiscuity, a peculiar feature of those cytokines, is a powerful and economic means of producing individual factors with distinct activities via different combinations of a single set of subunits. Whereas IL-12 and IL-23 have a clearly dominant immunostimulatory functional profile and IL-35 is a potent immunosuppressive agent, IL-27 can exert both adjuvant and regulatory effects, depending on the cytokine milieu. Promiscuity itself, however, may significantly hamper the therapeutic use of heterodimeric cytokines. The subunits of a recombinant cytokine, when administered in its native form, will rapidly dissociate in vivo and reassociate with alternative partners, thus generating different heterodimeric or even homodimeric molecules (i.e., p40/p40) with unwanted effects. As in other areas, bioengineering has provided a formidable tool to overcome the constraints associated with the potential use of IL-12 family cytokines. The generation of several gene constructs expressing IL-12, IL-23, IL-27, IL-35, or even the homodimer p40/p40, in their monomerized, single-chain form has allowed us to unveil the efficacy of those molecules in several experimental settings, including neoplasia, viral infection, chronic inflammation, allergy and autoimmunity. Although work is still needed to obtain an overall picture of therapeutic vs. adverse effects of individual molecules before any use in humans, the new frontiers of bioengineering are now driving the production of completely new combinations of cytokine subunits that may further extend the potential clinical use of such eclectic proteins.

白介素12（IL-12）家族包含一组异二聚体细胞因子，可以根据微环境的需要应对多种免疫状况。通过共享细胞因子和受体亚基，IL-12（由p40 / p35亚基组成），IL-23（p40 / p19），IL-27（p28 / EBI3）和IL-35（p35 / EBI3）表示为总体而言，这是一种高度通用的系统，可参与控制从炎症到耐受的连续过程。混杂是那些细胞因子的特有特征，是通过一组亚基的不同组合产生具有不同活性的个体因子的有力且经济的手段。IL-12和IL-23具有明显的主要免疫刺激功能特征，IL-35是有效的免疫抑制剂，而IL-27可以发挥辅助作用和调节作用，具体取决于细胞因子环境。然而，滥交本身可能会严重阻碍异二聚体细胞因子的治疗用途。以天然形式给药时，重组细胞因子的亚基将迅速解离体内并与其他配偶体重新缔合，从而产生不同的异二聚体甚至同二聚体分子（即p40 / p40），并产生不良影响。与其他领域一样，生物工程学提供了强大的工具来克服与潜在使用IL-12家族细胞因子相关的限制。以单体化单链形式表达IL-12，IL-23，IL-27，IL-35或同型二聚体p40 / p40的几种基因构建体的产生使我们能够揭示这些分子的功效几种实验设置，包括瘤形成，病毒感染，慢性炎症，过敏和自身免疫。尽管仍需要进行工作以获取单个分子在人类使用前的治疗效果与不良作用的全面概况，