PMID- 17931392
OWN - NLM
STAT- MEDLINE
DCOM- 20080219
LR  - 20240316
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 151
IP  - 1
DP  - 2008 Jan
TI  - Tumour necrosis factor-alpha blockade suppresses murine allergic airways 
      inflammation.
PG  - 114-22
AB  - Asthma is a heterogeneous disease that has been increasing in incidence 
      throughout western societies and cytokines, including proinflammatory tumour 
      necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of 
      asthma. Anti-TNF-alpha therapies have been established successfully in the clinic 
      for diseases such as rheumatoid arthritis and Crohn's disease. TNF-alpha-blocking 
      strategies are now being trialled in asthma; however, their mode of action is 
      poorly understood. Based on the observation that TNF-alpha induces lymph node 
      hypertrophy we have attempted to investigate this as a mechanism of action of 
      TNF-alpha in airway inflammation by employing two models of murine airway 
      inflammation, that we have termed short and long models, representing severe and 
      mild/moderate asthma, respectively. The models differ by their immunization 
      schedules. In the short model, characterized by eosinophilic and neutrophilic 
      airway inflammation the effect of TNF-alpha blockade was a reduction in draining 
      lymph node (DLN) hypertrophy, eosinophilia, interleukin (IL)-5 production and 
      immunoglobulin E (IgE) production. In the long model, characterized by 
      eosinophilic inflammation, TNF-alpha blockade produced a reduction in DLN 
      hypertrophy and IL-5 production but had limited effects on eosinophilia and IgE 
      production. These results indicate that anti-TNF-alpha can suppress DLN 
      hypertrophy and decrease airway inflammation. Further investigations showed that 
      anti-TNF-alpha-induced inhibition of DLN hypertrophy cannot be explained by 
      preventing l-selectin-dependent capture of lymphocytes into the DLN. Given that 
      overall TNF blockade was able to suppress the short model (severe) more 
      effectively than the long model (mild/moderate), the results suggest that 
      TNF-alpha blocking therapies may be more effective in the treatment of severe 
      asthma.
FAU - Hutchison, S
AU  - Hutchison S
AD  - Centre for Biophotonics, Strathclyde Institute of Pharmacy and Biomedical 
      Sciences, University of Strathclyde, Glasgow, UK. s.hutchison@strath.ac.uk
FAU - Choo-Kang, B S W
AU  - Choo-Kang BS
FAU - Bundick, R V
AU  - Bundick RV
FAU - Leishman, A J
AU  - Leishman AJ
FAU - Brewer, J M
AU  - Brewer JM
FAU - McInnes, I B
AU  - McInnes IB
FAU - Garside, P
AU  - Garside P
LA  - eng
PT  - Journal Article
DEP - 20071011
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9006-59-1 (Ovalbumin)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Adoptive Transfer/methods
MH  - Animals
MH  - Asthma/*immunology/pathology
MH  - Bronchial Hyperreactivity/immunology
MH  - Cytokines/*immunology
MH  - Eosinophilia
MH  - Etanercept
MH  - Flow Cytometry
MH  - Hypertrophy
MH  - Immunoglobulin G/*therapeutic use
MH  - Lung/*immunology/pathology
MH  - Lymph Nodes/immunology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Models, Animal
MH  - Ovalbumin
MH  - Receptors, Tumor Necrosis Factor/*therapeutic use
MH  - T-Lymphocytes/*immunology
MH  - Time
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
PMC - PMC2276921
EDAT- 2007/10/13 09:00
MHDA- 2008/02/20 09:00
PMCR- 2009/01/01
CRDT- 2007/10/13 09:00
PHST- 2007/10/13 09:00 [pubmed]
PHST- 2008/02/20 09:00 [medline]
PHST- 2007/10/13 09:00 [entrez]
PHST- 2009/01/01 00:00 [pmc-release]
AID - CEI3509 [pii]
AID - 10.1111/j.1365-2249.2007.03509.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2008 Jan;151(1):114-22. doi: 10.1111/j.1365-2249.2007.03509.x. 
      Epub 2007 Oct 11.