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.

Keywords: CpG-DNA, IFN-γ, IL-10, LPS, Ni-ion, Th1/Th2 balance.
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