PURPOSE:TNF-α is an important pro-inflammatory cytokine that is also a well known inducer of the inflammatory response and a regulator of immunity. A strong argument exists for TNF-α being a critical cytokine in the pathogenesis of chronic inflammatory disorders of the airways. Once released in the airways, TNF-α acts by inducing a general inflammatory response mainly through enhanced release of pro-inflammatory/chemotactic mediators and upregulation of adhesion molecules such as E-selectin, VCAM-1, and ICAM-1, thus facilitating the migration of neutrophils and eosinophils. To date there is very limited information on the use of TNF-α blocking agents in asthma. The present study investigated the effect of soluble TNF- α receptor on the airway inflammation in mice model of bronchial asthma.
METHODS:Female BALB/c mice were immunized by subcutaneous injection on days 0, 7, 14, and 21 with 25 μg of ovalbumin(OVA). Intranasal OVA challenges were administered on days 27, 29, and 31. Mice were treated with intraperitoneal soluble TNF-α receptor during the OVA challenge.
RESULTS:Mice exposed to OVA developed sustained eosinophilic airway inflammation and sustained AHR to methacholine compared with control mice. Intraperitoneal administration of soluble TNF-α receptor inhibited the development of airway hyperresponsiveness(AHR) and eosinophilic inflammation. The soluble TNF-α receptor treatment reduced IL-4, IL-5, IL-13 and IL-10 level in bronchoalveolar lavage fluid. Moreover, VCAM-1 expression on lung tissue was inhibited by soluble TNF-α receptor treatment.
CONCLUSION:The soluble TNF-α receptor can modulate the airway inflammation and AHR via inhibition of inflammatory cytokine production and adhesion molecule.
CLINICAL IMPLICATIONS:Theses results suggest that soluble TNF-α receptor is useful in patients with asthma, especially severe asthma.
DISCLOSURE:Sung Hak Park, No Financial Disclosure Information; No Product/Research Disclosure Information