Roles of TNF-α and IgE in the late phase of contact hypersensitivity induced by trimellitic anhydride

Trimellitic anhydride (TMA) is widely used industrially to make epoxy and alkyd resins, plasticizers and surfactants. The purpose of this study was to investigate whether contact hypersensitivity (CHS) is induced by repeated TMA challenge and the role of TNF-α and IgE in the TMA-induced CHS. The repetition of the challenge enlarged the extent of an early and a late phase of CHS in TNF-α^+/+ (B6129SF2/J) and Balb/c mice. In the late phase of TMA-induced CHS, the peak of ear swelling responses by single challenge showed at 24 h after challenge, but the peak was observed at 8 h after repeated challenge. In the TNF-α knockout TNF-α^+/+ (86;129S-Tnf^tm1Gk1) mice, the repetition of the TMA challenges enlarged the extent of the late phase of CHS, but less than those in TNF-α^+/+ mice. Injection of anti-TNF-α antibody into the peritoneal cavity of Balb/c mice significantly decreased the extent of the late phase of CHS. Subcutaneous injection of anti-IgE antibody into Balb/c mice also decreased the extent of the late phase of CHS in dose-dependent manner. Histologically, infiltration of polymorphonuclear leukocytes and eosinophils was more pronounced in repeatedly TMA-challenged TNF-α^+/+ and Balb/c mice than in the TNF-α^-/- mice and anti-TNF-α or anti-IgE antibodies treated Balb/c mice. These results indicate that mice sensitized by TMA could possibly offer a useful model to study the mechanism of CHS, and TNF-α and IgE may act as potential modulators in the late phase of TMA-induced CHS. Neutralization of TNF-α and IgE by anti-TNF-α or anti-IgE antibodies may provide therapeutic tools for the treatment of TMA-induced CHS.