Knoblock K F, Canning P C
Pfizer Inc., Central Research Division, Animal Health Research Department, Terre Haute, Indiana 47808.
Immunology. 1992 Jun;76(2):299-304.
In order to understand better how cytokines modulate porcine lymphocyte-mediated natural cytotoxicity and to develop a rapid and reliable colorimetric assay to study that activity in young pigs, we studied inherent and cytokine induced in vitro natural killer (NK) activity. The cytokines we studied were human recombinant interleukin-1 alpha (IL-1 alpha), IL-2, IL-4 and interferon-gamma (IFN-gamma). Natural killer activity by peripheral blood mononuclear cells (PBMC), reported as per cent specific lysis (%SL), was determined by the colorimetric measurement of lactate dehydrogenase released from tumour cell targets, YAC-1 and K562. Inherent NK activity was low and remained relatively unchanged by alterations of assay length or effector cell concentration. Low NK activity was also observed in response to IL-4 and IFN-gamma. IL-2 and, to a lesser extent, IL-1 alpha induced significant NK activity with trends towards increasing %SL with increasing cytokine dose. Optimal IL-1 alpha- and IL-2-induced NK activity could be observed at 18 hr, with significant activity stimulated by IL-2 as early as 4 hr. IL-2-induced NK activity was sensitive to effector cell concentration; %SL decreased as the effector to target ratio decreased. IL-1 alpha- and IL-2-induced NK activities were decreased in the presence of IL-4. These results indicate porcine PBMC are sensitive to in vitro modulation by human recombinant IL-1 alpha, IL-2 and IL-4. The ability of IL-1 alpha and IL-2 to induce swine NK activity and the ability of IL-4 to inhibit that activity are similar to the actions of those cytokines in human NK systems.
为了更好地理解细胞因子如何调节猪淋巴细胞介导的自然细胞毒性，并开发一种快速可靠的比色法来研究幼猪的这种活性，我们研究了固有和细胞因子诱导的体外自然杀伤（NK）活性。我们研究的细胞因子为人重组白细胞介素-1α（IL-1α）、IL-2、IL-4和干扰素-γ（IFN-γ）。外周血单个核细胞（PBMC）的自然杀伤活性以特异性裂解百分比（%SL）表示，通过比色法测量从肿瘤细胞靶标YAC-1和K562释放的乳酸脱氢酶来确定。固有NK活性较低，并且随着检测时间或效应细胞浓度的改变相对保持不变。对IL-4和IFN-γ的反应也观察到低NK活性。IL-2以及在较小程度上IL-1α诱导了显著的NK活性，随着细胞因子剂量增加，%SL有增加的趋势。在18小时时可观察到最佳的IL-1α和IL-2诱导的NK活性，IL-2早在4小时就刺激了显著的活性。IL-2诱导的NK活性对效应细胞浓度敏感；随着效应细胞与靶标比例降低，%SL下降。在IL-4存在的情况下，IL-1α和IL-2诱导的NK活性降低。这些结果表明猪PBMC对人重组IL-1α、IL-2和IL-4的体外调节敏感。IL-1α和IL-2诱导猪NK活性的能力以及IL-4抑制该活性的能力与这些细胞因子在人NK系统中的作用相似。
