Cytokine modulation in sepsis and septic shock

被引：93

作者：

Zanotti, S ^{[1
]}

Kumar, A

机构：

[1] Rush Med Coll, Rush Presbyterian St Lukes Med Ctr, Immunol Sect, Sect Crit Care Med, Chicago, IL 60612 USA

[2] Univ Manitoba, Sect CCM, Winnipeg, MB R3T 2N2, Canada

来源：

EXPERT OPINION ON INVESTIGATIONAL DRUGS | 2002年 / 11卷 / 08期

关键词：

G-CSF; IFN-gamma; IL-1; IL-1ra; IL-10; sepsis; septic shock; TGF-beta; TNF-alpha;

D O I：

10.1517/13543784.11.8.1061

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Sepsis and septic shock are a major cause of morbidity and mortality in patients admitted to the intensive care unit. Since the introduction of antibiotic therapy, the mortality associated with sepsis has remained within the 30-50% range. Sepsis constitutes the systemic response to infection. This response encompasses both pro-inflammatory and anti-inflammatory phases that are marked by the sequential generation of pro- and anti-inflammatory cytokines. Among the most important pro-inflammatory cytokines are TNF-alpha and IL-1beta. The pro-inflammatory effects of such cytokines are inhibited by soluble receptors/receptor antagonists and anti-inflammatory cytokines including IL-10 and transforming growth factor-beta. Modulation of the activity of both pro- and anti-inflammatory cytokines to improve outcome in patients with sepsis has been subject of multiple clinical studies. This review will examine clinical trials evaluating several strategies for blocking or attenuating TNF-alpha and IL-1beta activity. This review will also survey the current state of experimental therapies involving IL-10, transforming growth factor-beta, granulocyte colony-stimulating factor and IFN-gamma. Finally, newer developments related to less known cytokines such as macrophage migration inhibitory factor and high mobility group 1 protein will be evaluated.

引用

页码：1061 / 1075

页数：15

共 137 条

[1] EFFICACY AND SAFETY OF MONOCLONAL-ANTIBODY TO HUMAN TUMOR-NECROSIS-FACTOR-ALPHA IN PATIENTS WITH SEPSIS SYNDROME - A RANDOMIZED, CONTROLLED, DOUBLE-BLIND, MULTICENTER CLINICAL-TRIAL [J].

ABRAHAM, E ;

WUNDERINK, R ;

SILVERMAN, H ;

PERL, TM ;

NASRAWAY, S ;

LEVY, H ;

BONE, R ;

WENZEL, RP ;

BALK, R ;

ALLRED, R ;

PENNINGTON, JE ;

WHERRY, JC .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 273 (12) :934-941

[2]

Abraham E, 1998, LANCET, V351, P929

[3] p55 tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock - A randomized controlled multicenter trial [J].

Abraham, E ;

Glauser, MP ;

Butler, T ;

Garbino, J ;

Gelmont, D ;

Laterre, PF ;

Kudsk, K ;

Bruining, HA ;

Otto, C ;

Tobin, E ;

Zwingelstein, C ;

Lesslauer, W ;

Leighton, A .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 277 (19) :1531-1538

[4] Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: A randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients [J].

Abraham, E ;

Laterre, PF ;

Garbino, J ;

Pingleton, S ;

Butler, T ;

Dugernier, T ;

Margolis, B ;

Kudsk, K ;

Zimmerli, W ;

Anderson, P ;

Reynaert, M ;

Lew, D ;

Lesslauer, W ;

Passe, S ;

Cooper, P ;

Burdeska, A ;

Modi, M ;

Leighton, A ;

Salgo, M ;

Van der Auwera, P .

CRITICAL CARE MEDICINE, 2001, 29 (03) :503-510

[5] Experimental and emerging therapies for sepsis and septic shock [J].

Añel, RL ;

Kumar, A .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2001, 10 (08) :1471-1485

[6] IL-10 mediation of activation-induced Th1 cell apoptosis and lymphoid dysfunction in polymicrobial sepsis [J].

Ayala, A ;

Chung, CS ;

Song, GY ;

Chaudry, IH .

CYTOKINE, 2001, 14 (01) :37-48

[7]

Baumhofer JM, 1998, EUR J IMMUNOL, V28, P610, DOI 10.1002/(SICI)1521-4141(199802)28:02<610::AID-IMMU610>3.3.CO

[8]

2-X

[9] The tumor necrosis factor ligand and receptor families [J].

Bazzoni, F ;

Beutler, B .

NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (26) :1717-1725

[10]

BERNARD G, 2001, NEW ENGL J MED, V344, P749

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