Promotion of Nickel (Ni) Allergy by Anamnestic Sensitization with a Bacterial Component, Lipopolysaccharide (LPS), in Mice

Lipopolysaccharides (LPS) promote allergic responses to nickel (Ni) both in the sensitization and elicitation steps. In this study, we examine the effect of pre-sensitization to LPS on the occurrence of Ni allergy using a mouse model.

A 100 mg of LPS was injected into C57BL/6J mice intraperitoneally (ip). Three weeks later, the mice were subsequently injected with 0.3 μ moles of nickel dichloride (NiCl₂) and 100 μg of CpG-DNA, which acted as an adjuvant. The mice were repeatedly immunized with the 0.3 μg of nickel sulfate (NiSO₄), along with 300 μl of the adjuvant, Inject Alum (Pierce, USA). Then we examined the producing capabilities of T helper type 1 (Th1) and 2 (Th2) cytokines (interferon-gamma- (IFN)-γ and interleukin (IL)-10, respectively) from anti CD3 antibody-stimulated spleen cells.

Pre-treatment with LPS, followed by repeated challenges with Ni²⁺ and adjuvants significantly enhanced the IFN-γ-producing capability of spleen cells (n=5, p<0.01); however, that could not enhance the capability of spleen cells by a single challenge with Ni²⁺ and adjuvants (n=5). In contrast, without LPS treatment, single or even repeated challenges by Ni²⁺ could not enhance the IFN-γ-producing capability. On the other hand, the IL-10-producing capability of spleen cells was not enhanced even by LPS and repeated challenges with Ni²⁺ and adjuvants.

The solitary pre-sensitization to LPS is essential for the onset of Ni allergy by shifting the Th1/Th2 immune balance toward a Th1 dominant.