LPS inhalation challenge: a new tool to characterize the inflammatory response in humans

被引:21
作者
Kitz, Richard [1 ]
Rose, Markus A. [1 ]
Placzek, Katja [1 ]
Schulze, Johannes [1 ]
Zielen, Stefan [1 ]
Schubert, Ralf [1 ]
机构
[1] Goethe Univ Frankfurt, Childrens Hosp, Dept Pulmonol Allergol, D-60590 Frankfurt, Germany
关键词
bronchial hyperreactivity; experimental endotoxin inhalation; safety; repeatability;
D O I
10.1007/s00430-007-0053-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 [免疫学];
摘要
Inhaling bacterial endotoxin and its derivative LPS can induce a distinct inflammatory response, varying among hosts. Experimental LPS-inhalation is an established procedure in inflammation research. We evaluated experimental LPS-inhalation in 20 young healthy volunteers to determine the safety and the reproducibility of markers of inflammation and clinical findings (symptoms, lung function, exhalative NO, and body temperature). LPS was increased every 30 min up to cumulative 100 mu g, the protocol was repeated after 2, 4, and 6 weeks. During 71 provocations, 13 episodes of clinical complaints were observed in 10 subjects. Those were a total of 11 local reactions (15.5%, e. g., cough), and six systemic reactions (8.5%, e. g., fatigue). All adverse events resolved spontaneously within 10 h. Changes of FEV1 and eNO showed no significant differences between the four visits. In the majority of our subjects (88.2% on visit 1-3, 76.5% on visit 4), a rise in body temperature (> 0.5 degrees C) was recorded and normalised latest after 24 h. On the first and the last visit, serum concentrations of CrP and LBP increased significantly and correlated well with each other (r = 0.71; P < 0.001). LPS-challenge is a safe and tolerable tool to investigate inflammatory response in humans and could lead to better characterization of patients with chronic inflammatory disease.
引用
收藏
页码:13 / 19
页数:7
相关论文
共 27 条
[1]
Transgenic mice expressing rabbit C-Reactive protein exhibit diminished chemotactic factor-induced alveolitis [J].
Ahmed, N ;
Thorley, R ;
Xia, DY ;
Samols, D ;
Webster, RO .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 153 (03) :1141-1147
[2]
CD14-dependent airway neutrophil response to inhaled LPS: Role of atopy [J].
Alexis, N ;
Eldridge, M ;
Reed, W ;
Bromberg, P ;
Peden, DB .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2001, 107 (01) :31-35
[3]
[Anonymous], 1999, Am J Respir Crit Care Med, V160, P2104
[4]
STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT [J].
BLAND, JM ;
ALTMAN, DG .
LANCET, 1986, 1 (8476) :307-310
[5]
LPS binding protein is important in the airway response to inhaled endotoxin [J].
Brass, DM ;
Savov, JD ;
Whitehead, GS ;
Maxwell, AB ;
Schwartz, DA .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2004, 114 (03) :586-592
[6]
An essential role for lipopolysaccharide-binding protein in pulmonary innate immune responses [J].
Fan, MH ;
Klein, RD ;
Steinstraesser, L ;
Merry, AC ;
Nemzek, JA ;
Remick, DG ;
Wang, SC ;
Su, GL .
SHOCK, 2002, 18 (03) :248-254
[7]
Elements of immunity - The instructive role of innate immunity in the acquired immune response [J].
Fearon, DT ;
Locksley, RM .
SCIENCE, 1996, 272 (5258) :50-54
[8]
Lipopolysaccharide-binding protein is required to combat a murine Gram-negative bacterial infection [J].
Jack, RS ;
Fan, XL ;
Bernheiden, M ;
Rune, G ;
Ehlers, M ;
Weber, A ;
Kirsch, G ;
Mentel, R ;
Furll, B ;
Freudenberg, M ;
Schmitz, G ;
Stelter, F ;
Schutt, C .
NATURE, 1997, 389 (6652) :742-745
[9]
Grain dust and endotoxin inhalation challenges produce similar inflammatory responses in normal subjects [J].
Jagielo, PJ ;
Thorne, PS ;
Watt, JL ;
Frees, KL ;
Quinn, TJ ;
Schwartz, DA .
CHEST, 1996, 110 (01) :263-270
[10]
Systemic and bronchial inflammation following LPS inhalation in asthmatic and healthy subjects [J].
Kitz, Richard ;
Rose, Markus A. ;
Borgmann, Alexandra ;
Schubert, Ralf ;
Zielen, Stefan .
JOURNAL OF ENDOTOXIN RESEARCH, 2006, 12 (06) :367-374