TNF alpha is important in human lung allergic reactions

Area of Science:

• Immunology
• Respiratory Medicine
• Cell Biology

Background:

• Tumor necrosis factor alpha (TNF alpha) is a cytokine implicated in allergic respiratory reactions.
• Mast cells and eosinophils release TNF alpha, promoting mediator release and granulocyte migration.

Purpose of the Study:

• To investigate TNF alpha production in IgE-mediated allergic responses in human lungs.
• To determine if TNF alpha levels are sufficient to induce granulocyte migration.
• To identify cells expressing TNF alpha mRNA during these responses.

Main Methods:

• Human lung fragments were treated with anti-IgE to induce an IgE-mediated response.
• Histamine release and chemotactic activity were measured.
• TNF alpha levels and mRNA expression were assessed using ELISA and in situ hybridization.
• The effect of anti-TNF alpha antibody on neutrophil migration was evaluated.

Main Results:

• Anti-IgE treatment significantly increased histamine release and generated chemotactic activity for neutrophils and eosinophils.
• TNF alpha levels increased significantly post anti-IgE treatment, with measured concentrations inducing neutrophil transendothelial migration.
• Anti-TNF alpha antibody partially inhibited neutrophil chemotactic activity.
• In situ hybridization revealed an increase in TNF alpha mRNA-positive cells, including eosinophils, after anti-IgE stimulation.

Conclusions:

• IgE-mediated responses in human lungs release TNF alpha at biologically significant levels, promoting granulocyte chemotaxis.
• Eosinophils and other cells upregulate TNF alpha mRNA during IgE-mediated allergic reactions.
• TNF alpha is suggested to be a key effector molecule in the pathogenesis of allergic respiratory diseases.