The soluble tumor necrosis factor-alpha receptor suppresses airway inflammation in a murine model of acute asthma.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-alpha blocking strategies are now being tried in asthma patients. This study investigated whether TNF-alpha blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-alpha blocking therapy on cytokine production and adhesion molecule expression.


METHODS
Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-alpha receptor (sTNFR) during the OVA challenge.


RESULTS
There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue.


CONCLUSIONS
These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.
Nam
Hae-Seong
HS
Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Lee
Sook Young
SY
Kim
Seung Jun
SJ
Kim
Ju Sang
JS
Kwon
Soon Seog
SS
Kim
Young Kyoon
YK
Kim
Kwan Hyung
KH
Moon
Hwa Sik
HS
Song
Jeong Sup
JS
Park
Sung Hak
SH
Kim
Seok Chan
SC
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D015153:Blotting, Western; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D018927:Anti-Asthmatic Agents; D018793:Interleukin-13; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D010047:Ovalbumin