One important feature of the Propionibacterium acnes-induced hypersensitivity to LPS is the enhanced production of TNFα induced in the sensitized mice upon LPS challenge [Katschinski T., Galanos G., Coumbos A., Freudenberg M.A. Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice. Infect Immun 1992; 60: 1994-2001]. We investigated the role of LPS binding protein (LBP) in the TNFα response of normal and P. acnes-sensitized mice to LPS in LBP+/+ and LBP-/- mice. Treatment of LBP+/+ (BalbC and 129 Sv) mice with P. acnes enhanced their TNFα response to LPS by 75-200-fold compared to the non-treated controls. Unsensitized LBP-/- (129 Sv x BalbC) mice were also stimulated by LPS to produce low amounts of TNFα. These were enhanced by prior P. acnes treatment, however, only by a factor of 4. The characteristic TNFα hyper-response was absent suggesting that the enhanced activity of LPS in sensitized mice is expressed only in the presence of LBP. Evidence for this was obtained by showing that administration of exogenous LBP restored fully the inducibility of the TNFα hyper-response in P. acnes-sensitized LBP-/- mice. Their response to LPS was 1000-fold higher then that of sensitized controls without LBP. A similar LBP treatment of unsensitized LBP-/- mice increased the TNFα response by a factor of only 5. In an analogous experiment, also IFN-γ-sensitized LBP-/- mice exhibited a TNFα overproduction in response to LPS only in the presence of exogenous LBP.
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