TNF-alpha enhanced allergic sensitization to house dust mite in brown Norway rats

Ile have recently demonstrated that pulmonary exposure to residual oil fly ash (ROFA) resulted in enhanced sensitization to house dust mite (HDM) and augmented the development of allergic lung disease after allergen challenge . This effect was associated with increased tumor necrosis factor alpha (TA T-alpha), a macrophage- and epithelial cell-derived cytokine that promotes granulocyte migration to the lung. The present study examined whether exoge nous administration Of TNF-alpha enhances sensitization to HDM. One day pri or to pulmonary sensitization with 10 mug HDM (5 mug each on days I and 3), female Brown Norway rats were instilled via the trachea with either 2.0 mu g recombinant rat TNF-alpha, 2.0 mug bovine serum albumin (BSA), or 1000 mu g ROFA, and were challenged with 10 mug HDM 14 days later. Antigen-induced immediate bronchoconstriction responses, antigen-specific immunoglobulin E (IgE) titers, lymphocyte proliferation, cytokines (TAT-alpha and interleuki n [IL]-13), and eosinophils were elevated in rats treated with ROFA or TNF- alpha compared with BSA-treated controls after HDM challenge. Intratracheal administration of anti-TNF-alpha monoclonal antibody during ROFA exposure did not reduce ROFA-enhanced lymphocyte proliferation or IgE liters, but ha d a trend for reduced pulmonary inflammation. P is study demonstrates that TNF-alpha has similar adjuvant activity as ROFA, but other factors may fulf ill this function when TNF-alpha activity is blocked.