Jung T, Wagner K, Neumann C, Heusser C H
Department of Dermatology, University of Göttingen, Germany.
Eur J Immunol. 1999 Mar;29(3):864-71. doi: 10.1002/(SICI)1521-4141(199903)29:03<864::AID-IMMU864>3.0.CO;2-T.
The recombinant form of the extracellular domain of the IL-4 receptor (sIL-4R) is a potential candidate to neutralize IL-4; however, murine sIL-4R displayed both antagonistic and agonistic activity in vivo. Here we show that human recombinant sIL-4R induced the formation of complexed IL-4 in supernatants of activated T cells in a dose-dependent manner as measured by newly developed enzyme-linked immunosorbent assays. These IL-4/sIL-4R complexes liberated free IL-4 even after prolonged culturing. In contrast, in the absence of exogenously added sIL-4R, free IL-4 was rapidly consumed or proteolytically degraded in cultures of activated T cells. Thus, no IL-4 bioactivity could be determined in supernatants of T cells activated in the presence of IL-4 for 6 days. In contrast, the same cultures carried out in the presence of sIL-4R showed marked IL-4 bioactivity. While low concentrations of sIL-4R enhanced IL-4-driven inhibiton of IFN-gamma production by activated T cells, higher concentrations neutralized IL-4. Together, human sIL-4R, besides its activity as an antagonist to IL-4, also possesses protective and agonistic functions for IL-4, which may be relevant for clinical studies aiming to neutralize IL-4 in vivo.
白细胞介素4受体（sIL-4R）细胞外结构域的重组形式是中和白细胞介素4的潜在候选物；然而，小鼠sIL-4R在体内表现出拮抗和激动活性。在这里，我们表明，通过新开发的酶联免疫吸附测定法测量，人重组sIL-4R以剂量依赖的方式诱导活化T细胞上清液中形成复合白细胞介素4。即使经过长时间培养，这些白细胞介素4/sIL-4R复合物也能释放游离白细胞介素4。相比之下，在没有外源添加sIL-4R的情况下，游离白细胞介素4在活化T细胞培养物中迅速被消耗或被蛋白水解降解。因此，在白细胞介素4存在下活化6天的T细胞上清液中无法测定白细胞介素4的生物活性。相比之下，在sIL-4R存在下进行的相同培养显示出明显的白细胞介素4生物活性。虽然低浓度的sIL-4R增强了活化T细胞对白细胞介素4驱动的γ干扰素产生的抑制作用，但较高浓度则中和了白细胞介素4。总之，人sIL-4R除了作为白细胞介素4的拮抗剂发挥作用外，还对白细胞介素4具有保护和激动功能，这可能与旨在体内中和白细胞介素4的临床研究相关。
