Espinoza-Delgado I, Bosco M C, Musso T, Gusella G L, Longo D L, Varesio L
Macrophage Cell Biology Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland.
J Leukoc Biol. 1995 Jan;57(1):13-9. doi: 10.1002/jlb.57.1.13.
The recognition of the monocyte/macrophage-activating properties of IL-2 has broadened our image of the biological effects of this lymphokine from those of a T cell growth factor to those of a molecule with pleiotropic effects. The detailed analysis of the mechanisms of action of IL-2 including its biological effects on different cell types and the regulation of its receptors has increased dramatically the spectrum of the biological responses that can be modified by IL-2. The regulation of the expression of the IL-2 receptor subunits differs in terms of response to extracellular stimuli and intracellular control, suggesting that the response to IL-2 will vary depending on the nature and extent of environmental stimulation. Furthermore, the fact that the IL-2R gamma chain can be part of the receptor for IL-4, IL-7, and perhaps other cytokines indicates that IL-2 may modulate the response of monocytes simply by binding or releasing the IL-2R gamma chain and thus modulating the responsiveness to IL-4 or IL-7. Conversely, the extent of utilization of IL-2R gamma chain by various cytokines may dictate the monocytic response to IL-2. In fact, the availability of IL-2R gamma chain seems to be the limiting factor in the response of monocytes to IL-2. Modulation of cytokine receptors is an integral part of the control of the IL-2 response. The induction of CSF-1 receptor by IL-2 and the positive effect of CSF-1 on the duration of the cytotoxic response in IL-2-stimulated monocytes are an interesting example of a synergistic interaction of potential physiological relevance. The response of monocytes to IL-2 can also be modulated by inhibitory circuits, such as those involving TGF-beta 1, IFN-gamma, and IL-4. However, IFN-gamma and IL-4 can also activate monocytes and the timing and relative concentrations of the various cytokines may be critical variables in determining the ultimate monocyte phenotype. These studies have given us a glimpse of a very complex picture composed of multiple backgrounds and several players. However, the present information is not sufficient to make meaningful predictions of the resulting monocyte phenotype in an inflammatory reaction in which multiple cytokines are involved.(ABSTRACT TRUNCATED AT 400 WORDS)
白细胞介素-2（IL-2）具有单核细胞/巨噬细胞激活特性这一发现，拓宽了我们对这种淋巴因子生物学效应的认识，使其从一种T细胞生长因子转变为具有多效性作用的分子。对IL-2作用机制的详细分析，包括其对不同细胞类型的生物学效应及其受体的调节，极大地扩展了可被IL-2改变的生物学反应谱。IL-2受体亚基表达的调节在对细胞外刺激的反应和细胞内控制方面存在差异，这表明对IL-2的反应将因环境刺激的性质和程度而异。此外，IL-2Rγ链可成为IL-4、IL-7以及可能其他细胞因子受体的一部分，这表明IL-2可能通过结合或释放IL-2Rγ链来调节单核细胞的反应，从而调节对IL-4或IL-7的反应性。相反，各种细胞因子对IL-2Rγ链的利用程度可能决定单核细胞对IL-2的反应。事实上，IL-2Rγ链的可用性似乎是单核细胞对IL-2反应的限制因素。细胞因子受体的调节是IL-2反应控制的一个组成部分。IL-2诱导集落刺激因子-1（CSF-1）受体以及CSF-1对IL-2刺激的单核细胞细胞毒性反应持续时间的积极作用，是潜在生理相关性协同相互作用的一个有趣例子。单核细胞对IL-2的反应也可被抑制性回路调节，例如涉及转化生长因子-β1（TGF-β1）、干扰素-γ（IFN-γ）和IL-4的回路。然而，IFN-γ和IL-4也可激活单核细胞，各种细胞因子的作用时间和相对浓度可能是决定最终单核细胞表型的关键变量。这些研究让我们瞥见了一幅由多种背景和多个参与者组成的非常复杂的图景。然而，目前的信息不足以对涉及多种细胞因子的炎症反应中产生的单核细胞表型做出有意义的预测。（摘要截选至400字）
