目的:探讨白细胞介素(interleukin,IL)-12p40、干扰素(interferon,IFN)-γ在缓解复发型多发性硬化(relap-sing remitting form of multiple sclerosis,RRMS)发病中的病生机制。方法:选取RRMS急性期患者24例及作为对照组的非炎性神经系...目的:探讨白细胞介素(interleukin,IL)-12p40、干扰素(interferon,IFN)-γ在缓解复发型多发性硬化(relap-sing remitting form of multiple sclerosis,RRMS)发病中的病生机制。方法:选取RRMS急性期患者24例及作为对照组的非炎性神经系统疾病(non-inflammatory neurological diseases,NIND)患者12例,应用ELISA法测定受试者血清及脑脊液中IL-12p40、IFN-γ水平。结果:RRMS组血清中IL-12p40水平明显下降,IFN-γ水平与NIND组相比无统计学意义。脑脊液中IL-12p40、IFN-γ水平在两组中可检测到的阳性例数均低,相比之下无统计学意义。结论:IL-12p40参与了多发性硬化发病的免疫病理过程。展开更多
therapeutic activity of a human monoclonal antibody to the human interleukin-12 p40 subunit (anti-IL12p40)has been established both in vitro and in vivo,warranting a first-in-human investigation in psoriasis. This pha...therapeutic activity of a human monoclonal antibody to the human interleukin-12 p40 subunit (anti-IL12p40)has been established both in vitro and in vivo,warranting a first-in-human investigation in psoriasis. This phase I, first-in-human, non-randomized, open-label study evaluated the short-term safety, pharmacokinetics, and clinical response of single, ascending, intravenous (IV) doses of anti-IL-12p40 in subjects with moderate-to-severe psoriasis vulgaris. Eighteen subjects with at least 3%body surface area involvement were enrolled infour dose groups (0.1, 0.3, 1.0, and 5.0 mg per kg). Safety, pharmacokinetics, and clinical response (e.g., Psoriasis Area and Severity Index (PASI)) were monitored at baseline and at specific time points over a 16-wk follow-up period. Anti-IL-12p40 was generally well tolerated. No related serious adverse events or infusion reactions were reported, and most adverse events were mild. IV anti-IL-12p40 yielded linear pharmacokinetics, with a mean terminal half-life of approximately 24 d. Dose-dependent associations with both the rate and extent of clinical response were observed across the four dose groups. Twelve of 18 subjects (67%) achieved at least a 75%improvement in PASI between 8 and 16 wk after study agent administration. Significant and sustained concentration-dependent improvements in psoriatic lesions were observed in most subjects.展开更多
In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain r...In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.展开更多
文摘目的:探讨白细胞介素(interleukin,IL)-12p40、干扰素(interferon,IFN)-γ在缓解复发型多发性硬化(relap-sing remitting form of multiple sclerosis,RRMS)发病中的病生机制。方法:选取RRMS急性期患者24例及作为对照组的非炎性神经系统疾病(non-inflammatory neurological diseases,NIND)患者12例,应用ELISA法测定受试者血清及脑脊液中IL-12p40、IFN-γ水平。结果:RRMS组血清中IL-12p40水平明显下降,IFN-γ水平与NIND组相比无统计学意义。脑脊液中IL-12p40、IFN-γ水平在两组中可检测到的阳性例数均低,相比之下无统计学意义。结论:IL-12p40参与了多发性硬化发病的免疫病理过程。
文摘therapeutic activity of a human monoclonal antibody to the human interleukin-12 p40 subunit (anti-IL12p40)has been established both in vitro and in vivo,warranting a first-in-human investigation in psoriasis. This phase I, first-in-human, non-randomized, open-label study evaluated the short-term safety, pharmacokinetics, and clinical response of single, ascending, intravenous (IV) doses of anti-IL-12p40 in subjects with moderate-to-severe psoriasis vulgaris. Eighteen subjects with at least 3%body surface area involvement were enrolled infour dose groups (0.1, 0.3, 1.0, and 5.0 mg per kg). Safety, pharmacokinetics, and clinical response (e.g., Psoriasis Area and Severity Index (PASI)) were monitored at baseline and at specific time points over a 16-wk follow-up period. Anti-IL-12p40 was generally well tolerated. No related serious adverse events or infusion reactions were reported, and most adverse events were mild. IV anti-IL-12p40 yielded linear pharmacokinetics, with a mean terminal half-life of approximately 24 d. Dose-dependent associations with both the rate and extent of clinical response were observed across the four dose groups. Twelve of 18 subjects (67%) achieved at least a 75%improvement in PASI between 8 and 16 wk after study agent administration. Significant and sustained concentration-dependent improvements in psoriatic lesions were observed in most subjects.
文摘In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.
