Shiratsuchi H, Johnson J L, Ellner J J
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
J Immunol. 1991 May 1;146(9):3165-70.
Certain cytokines including IFN-gamma possess macrophage-activating factor activity that enhances the ability of these effector cells to destroy intracellular pathogens. A panel of recombinant and highly purified human cytokines was screened to detect this effect on the activation of human monocytes to kill Mycobacterium avium in an in vitro model. Peripheral blood monocytes obtained from 15 healthy donors were precultured for 2 days before infection. Monocytes were infected with two strains of M. avium, one AIDS-associated and relatively avirulent strain (86m2096), and the other a non-AIDS-associated isolate that demonstrated consistent and rapid growth in cultured human monocytes (LR114F). The effects of recombinant and purified human cytokines on M. avium infection were assayed by determining CFU of M. avium in lysates of infected monocytes after 0, 4, and 7 days of culture. After infection, monocytes were cultured in medium alone or continuously in the presence of the following cytokines: IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IFN-gamma, granulocyte-macrophage-CSF, or macrophage-CSF. In some experiments, cultures were performed in the presence of indomethacin (IM) in addition to cytokines. Culture in the presence of rIFN-gamma was associated with a decrease in mycobacterial growth within human monocytes. The combination of 300 U/ml of IFN-gamma plus 1 micrograms/ml of IM was associated with a 10-fold decrease (p less than 0.01) in intracellular growth of the virulent strain (LR114F) compared with unstimulated cultures. No other cytokine or combination of a cytokine with IM inhibited the intracellular growth of either strain of M. avium in human monocytes. Rather, several cytokines enhanced the intracellular growth of M. avium. IL-3, IL-6, and macrophage-CSF increased the growth of one, and IL-1 alpha of both strains of M. avium tested. IL-1 alpha and IL-6 also induced M. avium growth in tissue culture medium without monocytes. These studies indicate bidirectional effects of cytokines on intracellular parasitism that may influence the outcome of M. avium infection.
某些细胞因子，包括γ干扰素，具有巨噬细胞激活因子活性，可增强这些效应细胞破坏细胞内病原体的能力。我们筛选了一组重组且高度纯化的人细胞因子，以在体外模型中检测其对人单核细胞激活以杀灭鸟分枝杆菌的作用。从15名健康供体获取的外周血单核细胞在感染前预培养2天。单核细胞用两株鸟分枝杆菌感染，一株与艾滋病相关且毒力相对较弱的菌株（86m2096），另一株是在培养的人单核细胞中显示出持续快速生长的非艾滋病相关分离株（LR114F）。通过测定培养0、4和7天后感染单核细胞裂解物中鸟分枝杆菌的菌落形成单位（CFU），来检测重组和纯化的人细胞因子对鸟分枝杆菌感染的影响。感染后，单核细胞单独在培养基中培养或在以下细胞因子存在下持续培养：白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-3（IL-3）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、γ干扰素（IFN-γ）；粒细胞-巨噬细胞集落刺激因子（GM-CSF）或巨噬细胞集落刺激因子（M-CSF）。在一些实验中，除细胞因子外，还在吲哚美辛（IM）存在下进行培养。在rIFN-γ存在下培养与人单核细胞内分枝杆菌生长减少有关。与未刺激的培养物相比，300 U/ml的IFN-γ加1μg/ml的IM组合使强毒株（LR114F）的细胞内生长减少了10倍（p<0.01）。没有其他细胞因子或细胞因子与IM的组合能抑制人单核细胞中任何一株鸟分枝杆菌的细胞内生长。相反，几种细胞因子增强了鸟分枝杆菌的细胞内生长。IL-３、IL-6和M-CSF增加了所测试的一株鸟分枝杆菌的生长，IL-1α增加了两株鸟分枝杆菌的生长。IL-1α和IL-6还在没有单核细胞的组织培养基中诱导鸟分枝杆菌生长。这些研究表明细胞因子对细胞内寄生具有双向作用，这可能会影响鸟分枝杆菌感染的结果。
