Chen Q, Daniel V, Maher D W, Hersey P
Immunology and Oncology Unit, Mater Misericordiae Hospital, Newcastle, NSW, Australia.
Int J Cancer. 1994 Mar 1;56(5):755-60. doi: 10.1002/ijc.2910560524.
Previous studies have shown that IL-10 may modulate immune responses towards the humoral arm by inhibiting production of cytokines involved in cell-mediated responses. In the present studies, we found that mRNA to IL-10 could be demonstrated in 66% of melanoma cell lines by PCR amplification of reverse-transcribed mRNA and in supernatants of the cell lines by ELISA. Release into the supernatants increased approximately 2-fold each day up to 3 days. The MW of 35S-labelled IL-10 secreted by melanoma cells was similar to that reported in previous studies. In the present studies we also examined whether IL-10 may be responsible for some of the immunosuppressive effects of the melanoma cell supernatants observed in previous studies, by testing whether MAbs against IL-10 could reverse the inhibitory effects of these supernatants. Recombinant IL-10 and melanoma supernatants were found to inhibit production of TNF-alpha, IFN-gamma, IL-2 and mixed lymphocyte reactions but reversal of these effects of melanoma supernatants by MAbs against IL-10 was only seen in the case of TNF-alpha production. These results extend the range of cell types known to produce IL-10 and indicate that malignancy of certain cell types may lead to unregulated production of IL-10 that could have the potential to modulate immune responses against the tumor.
先前的研究表明,IL-10可能通过抑制参与细胞介导反应的细胞因子的产生来调节针对体液免疫的免疫反应。在本研究中,我们发现通过逆转录mRNA的PCR扩增,在66%的黑色素瘤细胞系中可检测到IL-10的mRNA,并且通过ELISA在细胞系的上清液中也能检测到。释放到上清液中的量在3天内每天增加约2倍。黑色素瘤细胞分泌的35S标记的IL-10的分子量与先前研究报道的相似。在本研究中,我们还通过测试抗IL-10单克隆抗体是否能逆转这些上清液的抑制作用,来研究IL-10是否可能是先前研究中观察到的黑色素瘤细胞上清液的一些免疫抑制作用的原因。发现重组IL-10和黑色素瘤上清液可抑制TNF-α、IFN-γ、IL-2的产生以及混合淋巴细胞反应,但只有在TNF-α产生的情况下,抗IL-10单克隆抗体才能逆转黑色素瘤上清液的这些作用。这些结果扩展了已知产生IL-10的细胞类型范围,并表明某些细胞类型的恶性肿瘤可能导致IL-10的失控产生,并有可能调节针对肿瘤的免疫反应。