Modulation of ex vivo cytokine production by splenocytes using in vitro combined therapeutics in murine retroviral model.
Modulation of ex vivo cytokine production by splenocytes using in vitro combined therapeutics in murine retroviral model.
复制标题
在小鼠逆转录病毒模型中使用体外联合疗法调节脾细胞的离体细胞因子产生。
DOI：
10.1089/104454999315132
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Specter,SC
中科院分区：
文献类型：
--
作者：
Kang,LC;Kerben,MJ;Ugen,KE;Specter,SC
1型和2型细胞因子水平的改变在逆转录病毒诱导的免疫抑制中很重要。免疫刺激剂与抗病毒药物的结合改变了小鼠逆转录病毒感染的过程。此前研究表明，与单独使用AZT相比，体外治疗未感染的脾细胞和体内联合应用叠氮胸苷(AZT)和甲硫氨酸脑啡肽(MENK)治疗Friend白血病病毒(FLV)感染的小鼠可显著提高1型细胞因子水平和降低2型细胞因子水平。为了研究免疫调节起始时间对逆转录病毒感染过程的影响，我们检测了感染小鼠脾细胞产生细胞因子的动力学。用流感病毒感染BALB/c小鼠，在感染后不同时间(第1、3、7、10、14天)取脾细胞。用AZT、MENK或AZT+MENK处理小鼠脾细胞48h后，检测未刺激或ConA刺激的脾细胞产生IL-2、IL-4和IL-10的能力，随着ConA刺激和联合治疗，分离的脾细胞产生1型细胞因子IL-2和干扰素-γ的能力下降。这些结果表明，在感染过程的后期开始的MENK治疗不能调节细胞因子的分布，并且可能在改变FLV诱导的疾病的过程中无效。结果表明，在感染早期开始抗逆转录病毒治疗是必要的。这些信息可能适用于未来人类感染HIV-1的治疗方案的设计。
Altered levels of Type 1 and Type 2 cytokines are important in retrovirus-induced immunosuppression. The combination of immunostimulatory agents with antiviral drugs alters the course of murine retroviral infections. Previously, it was demonstrated that in vitro treatment of noninfected splenocytes and in vivo treatment of Friend leukemia virus (FLV)-infected mice with the combination of azidothymidine (AZT) and methionine enkephalin (MENK) significantly increases Type 1 cytokine levels and decreases Type 2 cytokines compared with treatment with only AZT. In order to study the effect of the time of initiation of immunomodulation on the course of retroviral infections, we examined the kinetics of cytokine production by isolated splenocytes from infected mice. BALB/c mice were infected with FLV, and spleen cells were removed at specified times postinfection (days 1, 3, 7, 10, and 14). Interleukin (IL)-2, interferon (IFN-gamma, IL-4, and IL-10 production by unstimulated or ConA-stimulated splenocytes treated in vitro with AZT, MENK, or AZT + MENK was determined after 48 h. The capacity of the isolated splenocytes to produce the Type 1 cytokines IL-2 and IFN-gamma in response to stimulation with ConA and combination therapy decreased over the course of infection. These results suggest that MENK treatment initiated later in the course of infection is unable to modulate the cytokine profile and would likely be ineffective in altering the course of FLV induced-disease. The results indicate the necessity to initiate antiretroviral therapy early in infection. Such information may be applicable in designing future regimens for HIV-1 infections in humans.