Cytokines play a significant role in the regulation ofToxoplasma gondii in the central nervous system. Cytokine-activated microglia are important host defense cells in central nervous system infections. Recent evidence indicates that astrocytes can also be activated by cytokines to inhibit intracellular pathogens. In this study, we examined the effect of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1 on the growth of T. gondii in a primary murine astrocyte culture. Pretreatment of astrocytes with IFN-γ resulted in 65% inhibition of T. gondii growth. Neither TNF-α, IL-1, nor IL-6 alone had any effect on T. gondii growth. IFN-γ in combination with either TNF-α, IL-1, or IL-6 caused a 75 to 80% inhibition of growth. While nitric oxide was produced by astrocytes treated with these cytokines, inhibition of T. gondiigrowth was not reversed by the addition of the nitric oxide synthase inhibitor N G-monomethyl-l-arginine. Furthermore, IFN-γ in combination with IL-1, IL-6, or TNF-α also induced inhibition in astrocytes derived from syngeneic mice deficient in the enzyme inducible nitric oxide synthase. This finding suggests that the mechanism of cytokine inhibition is not nitric oxide mediated. Similarly, the addition of tryptophan had no effect on inhibition, indicating that the mechanism was not mediated via induction of the enzyme indoleamine 2,3-dioxygenase. The mechanism of inhibition remains to be elucidated. Results from this study demonstrate that cytokine-activated astrocytes are capable of significantly inhibiting the growth of T. gondii. These data indicate that astrocytes may be important host defense cells in controlling toxoplasmosis in the brain.
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机译：细胞因子在中枢神经系统中对弓形虫的调节中起着重要作用。细胞因子激活的小胶质细胞是中枢神经系统感染中重要的宿主防御细胞。最近的证据表明，星形胶质细胞也可以被细胞因子激活以抑制细胞内病原体。在这项研究中，我们检查了γ干扰素（IFN-γ），肿瘤坏死因子α（TNF-α），白介素6（IL-6）和IL-1对 T生长的影响。刚地鼠星形胶质细胞培养中的刚地。用IFN-γ预处理星形胶质细胞导致65％的Tem抑制。刚地增长。单独的TNF-α，IL-1和IL-6都不会对 T产生任何影响。刚地增长。 IFN-γ与TNF-α，IL-1或IL-6的结合导致75-80％的生长抑制。虽然用这些细胞因子处理过的星形胶质细胞产生一氧化氮，但抑制了em。加入一氧化氮合酶抑制剂 N G -单甲基-1-精氨酸不会使刚地的生长逆转。此外，IFN-γ与IL-1，IL-6或TNF-α的结合也可诱导衍生自缺乏可诱导酶型一氧化氮合酶的同系小鼠的星形胶质细胞。该发现表明细胞因子抑制的机制不是一氧化氮介导的。类似地，色氨酸的添加对抑制没有影响，表明该机制不是通过吲哚胺2，3-二加氧酶的诱导而介导的。抑制机理尚待阐明。这项研究的结果表明，细胞因子激活的星形胶质细胞能够显着抑制 T的生长。刚地。这些数据表明，星形胶质细胞可能是控制脑弓形体病的重要宿主防御细胞。
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