目的：研究TNF-α对小鼠腹腔渗出细胞的激活和杀菌活性的效应。方法：以IL-12、IL-18、IFN-γ、TNF-α及抗体诱导小鼠腹腔渗出细胞和巨噬细胞，应用ELISA法测定细胞因子变化，Griess反应法测定培养上清液中NO的含量，检测巨噬细胞内新型隐球菌菌落数。结果：IL-12和IL-18联合应用协同诱导腹腔渗出细胞产生TNF-α，且能被IFN-γ抗体所抑制。IFN-γ、TNF-α协同诱导巨噬细胞产生N0和增强其杀伤新型隐球菌活性。结论：TNF-α在细胞因子相互调节诱导增强巨噬细胞杀真菌活性中起重要作用。

Objective To explore adverse effects of combined treatment of interleukin-12 (IL-12) and interleukin-18 (IL-18) against cryptococcosis in a murine model. Methods Infected mice were treated with a combination of IL-12 and IL-18. Their body weight and intake of water and food were observed and recorded. Serum levels of leptin were detected with an enzyme-linked immune sorbent assay (ELISA). Results In the combined treatment group, the intake volume of water and food were reduced, leading to weight loss and undetectable levels of leptin in the serum. These adverse effects were more profound in mice that had received higher doses of cytokines, which sometimes led to a fatal outcome. There was a significant difference compared with the control group. Neutralization of endogenous tumor necrosis factor-α (TNF-α) by its specific mAb did not alter the wasting effect of this treatment. Conclusions The combined IL-12/IL-18 treatment may cause a number of adverse effects independent of TNF-α and leptin synthesis. Further investigations for resolving these adverse effects are required before clinical application of these cytokines.