Combined therapy of interleukin-12 and interleukin-18 against Cryptococcus neoformans infection in a murine model  

作　　者：张天托 Kazuyoshi Kawakami Mahboob H Qureshi 唐英春 Atsushi Saito 

机构地区：[1]Department of Internal Medicine, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China [2]Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

出　　处：《Chinese Medical Journal》2003年第5期669-672,共4页中华医学杂志（英文版）

摘　　要：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 immuno 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.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 immuno 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.

关 键 词：adverse effect INTERLEUKIN-12 INTERLEUKIN-18 tumor necrosis factor-α CRYPTOCOCCOSIS 

分 类 号：R519[医药卫生—内科学]