北京大学学报(医学版) ›› 2019, Vol. 51 ›› Issue (6): 985-988. doi: 10.19723/j.issn.1671-167X.2019.06.001

• 专家笔谈 •    下一篇

低剂量白细胞介素-2在自身免疫性疾病治疗中的意义及前景

何菁,程功,栗占国()   

  1. 北京大学人民医院风湿免疫科,北京大学人民医院风湿免疫研究所,北京 100044
  • 收稿日期:2019-10-25 出版日期:2019-12-18 发布日期:2019-12-19
  • 通讯作者: 栗占国 E-mail:li99@bjmu.edu.cn

  • Received:2019-10-25 Online:2019-12-18 Published:2019-12-19

关键词: 白细胞介素-2, 自身免疫性疾病, 感染

中图分类号: 

  • R593.3

表1

已发表的低剂量IL-2治疗自身免疫性疾病的临床试验"

Diseases Daily dose/(Million IU) Clinical efficacy Immunological changes References
SLE 1 SLEDAI↓ Treg↑,Th17 ↓, Tfh↓,
NK↑,CD56brightNK↑
He et al.(2016,2019)[1,2]
SS 1.5 Not evaluated Treg↑,Th17↓ Miao et al.(2018)[22]
AS 0.5 BASDAI↓ Treg↑,Th17/Treg↓ An et al.(2019)[24]
DM/PM 0.5 CK↓ Treg↑ Zhang et al.(2019)[23]
GVHD 0.3/1/3 per m2 Rash↓ Treg↑ Betts et al.(2017)[15]
Zhao et al.(2016)[16]
HCV-induced vasculitis 1.5 Vasculitis↓ Treg↑,NK↑,CD56brightNK↑ Saadoun et al.(2011)[17]
T1DM 0.33/1/3 Not evaluated Treg↑ Hartemann et al.(2013)[18]
ITP 1 PLT↑ Treg↑ Zhang et al.(2018)[19, 20]
Alopecia areata 1.5 Hair loss area↓ Treg↑,Teff↓ Castela et al.(2014)[21]
11 kinds of autoimmune diseases such as RA 1 Effective Treg↑ Rosenzwajg et al.(2019)[3]

表2

已完成但尚未发表的低剂量IL-2治疗自身免疫性疾病的临床试验"

Disease Year Type Number Country
RA 2016 Single-center 47 China
SS 2016 Single-center 60 China
Multiple sclerosis 2016 Single-center 30 France
Hemolytic anemia 2017 Single-center 2 France
CKD 2016 Single-center 10 China
SLE 2017 Multi-center 100 France etc.
Amyotrophic lateral sclerosis 2015 Single-center 36 France
[1] He J, Zhang R, Shao M , et al. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: A randomised, double-blind, placebo-controlled trial[J/OL]. Ann Rheum Dis, 2019, 9(2019-09-19)[2019-10-01]. .
[2] He J, Zhang X, Wei Y , et al. Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus[J]. Nat Med, 2016,22(9):991-993.
[3] Rosenzwajg M, Lorenzon R, Cacoub P , et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial[J]. Ann Rheum Dis, 2019,78(2):209-217.
[4] Morgan DA, Ruscetti FW, Gallo R . Selective in vitro growth of T lymphocytes from normal human bone marrows[J]. Science, 1976,193(4257):1007-1008.
[5] Mizel SB, Farrar JJ . Revised nomenclature for antigen-nonspecific T-cell proliferation and helper factors[J]. Cell Immunol, 1979,48(2):433-436.
[6] Shao Q, Gao H,. Progress in interleukin-2 therapy for rheumatic immune diseases by regulating the immune balance of T cells[J/OL]. Scand J Immunol, 2019, 9(2019-09-08)[2019-10-01].
[7] Sakaguchi S, Wing K, Miyara M . Regulatory T cells: A brief history and perspective[J]. Eur J Immunol, 2007,37(Suppl 1):116-123.
[8] Harrington LE, Hatton RD, Mangan PR , et al. Interleukin 17-producing CD4+effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J]. Nat Immunol, 2005,6(11):1123-1132.
[9] Zhao Z, Zhang X, Su L , et al. Fine tuning subsets of CD4+T cells by low-dosage of IL-2 and a new therapeutic strategy for autoimmune diseases [J]. Int Immunopharmacol, 2018,56:269-276.
[10] Kim HS, Jang SW, Lee W , et al. PTEN drives Th17 cell differentiation by preventing IL-2 production[J]. J Exp Med, 2017,214(11):3381-3398.
[11] Osnes LT, Nakken B, Bodolay E , et al. Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and pri-mary immunodeficiencies: Novel tool for diagnostics and patient follow-up[J]. Autoimmun Rev, 2013,12(10):967-971.
[12] Li J, Lu E, Yi T , et al. EBI2 augments Tfh cell fate by promoting interaction with IL-2-quenching dendritic cells[J]. Nature, 2016,533(7601):110-114.
[13] Shao M, He J, Zhang R , et al. Interleukin-2 deficiency associated with renal impairment in systemic lupus erythematosus[J]. J Interferon Cytokine Res, 2019,39(2):117-124.
[14] Shin MS, Lee N, Kang I . Effector T-cell subsets in systemic lupus erythematosus: Update focusing on Th17 cells[J]. Curr Opin Rheumatol, 2011,23(5):444-448.
[15] Betts BC, Pidala J, Kim J , et al. IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation[J]. Haematologica, 2017,102(5):948-957.
[16] Zhao XY, Zhao XS, Wang YT , et al. Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study[J]. Oncoimmunology, 2016,5(12):e1250992.
[17] Saadoun D, Rosenzwajg M, Joly F , et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis[J]. N Engl J Med, 2011,365(22):2067-2077.
[18] Hartemann A, Bensimon G, Payan CA , et al. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial[J]. Lancet Diabetes Endocrinol, 2013,1(4):295-305.
[19] Zhang J, Ruan Y, Shen Y , et al. Low dose IL-2 increase regulatory T cells and elevate platelets in a patient with immune thrombocytopenia[J]. Cytometry B Clin Cytom, 2018,94(3):400-404.
[20] Zhang J, Ruan Y, Xu X , et al. Therapeutic potential of low-dose IL-2 in immune thrombocytopenia: An analysis of 3 cases[J]. Cytom B Clin Cytom, 2018,94(3):428-433.
[21] Castela E, Le Duff F, Butori C , et al. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata[J]. JAMA Dermatol, 2014,150(7):748-751.
[22] Miao M, Hao Z, Guo Y , et al. Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with pri-mary Sjögren’s syndrome[J]. Ann Rheum Dis, 2018,77(12):1838-1840.
[23] Zhang S, Wang J, Sun H , et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2[J/OL]. Ann Rheum Dis, 2019, 10(2019-10-14)[2019-10-16].
[24] An H, Li X, Li F , et al. The absolute counts of peripheral T lymphocyte subsets in patient with ankylosing spondylitis and the effect of low-dose interleukin-2[J]. Medicine (Baltimore), 2019,98(15):e15094.
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