Lipopolysaccharide promotes and augments metal allergies in mice, dependent on innate immunity and histidine decarboxylase

Background: Few adequate murine models exist for metal allergies, it being especially difficult to induce Ni allergy in mice. Objective: We examined the effect of lipopolysaccharide (LPS) on allergies to Ni and other metals in mice. Methods: Ten days after sensitization with a metal salt and LPS, the ears were challenged with the same metal salt. Results: LPS+NiCl₂ (1 mm) was effective at sensitizing mice to Ni, LPS being effective at very low concentrations whether injected intradermally or intraperitoneally. The ear-swelling response to Ni was more severe and more rapid in C57BL/6 mice than in BALB/c mice. In mast-cell-deficient mice, TNF-α-deficient mice, and interestingly even in nude (T cell deficient) mice, NiCl₂+LPS induced a Ni allergy similar in degree to that in the respective control mice, but it induced Ni allergy only weakly in TLR4-mutant mice, macrophage-depleted mice, and IL-1-deficient mice. The activity of the histamine-forming enzyme histidine decarboxylase (HDC) in the ears increased in parallel with ear swelling, and HDC-deficient mice were resistant to ear swelling. Challenge with NiCl ₂+LPS augmented ear swelling (vs. NiCl₂ alone). LPS induced effective sensitization to other metals (Cr, Co, Pd, or Ag). Conclusions: These results indicate that in mice, LPS is a very important inducer of metal allergies, and potently promotes them (dependent on both innate immunity and HDC induction in cells other than mast cells). We discussed the idea that the bacterial environment is important for the establishment of metal allergies and for their provocation, and that the current thinking (including the contribution of T cells) should be reappraised in future studies.