Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide

The potential role of respiratory infections in altering the development of atopy and asthma is complex. Infections have been suggested to be effectiv e in preventing the induction of T-helper 2-polarized allergen-specific imm unity in early life, but also to exacerbate asthma in older, sensitized ind ividuals. The mechanism(s) underlying these effects are poorly defined. The aim of this work was to determine the influence of lipopolysaccharide (LPS ) exposure on the development of sensitization to allergen and the response to allergen challenge in vivo. Piebald-Virol-Glaxo rats were exposed to a single aerosol of LPS 1 d before or 1, 2, 4, 6, 8, or 10 d after sensitizat ion with ovalbumin (OVA). On Day 11 animals were exposed to 1% OVA and resp onses to allergen were measured 24 h later, monitoring inflammatory cell in flux and microvascular leakage into bronchoalveolar lavage (BAL) fluid as w ell as pulmonary responses to methacholine using the forced oscillation tec hnique. Histologic analysis was included to complement the BAL results. Sin gle aerosol exposure to LPS 1 d before and up to 4 d after intraperitoneal injection of OVA protected against the development of OVA-specific immunogl obulin tig) E. LPS exposure 6, 8, or 10 d after sensitization further exace rbated the OVA-induced cellular influx, resulting in neutrophilia and incre ased Evans Blue dye leakage with no effect on serum IgE levels. In addition , LPS abolished the OVA-induced hyperresponsiveness in sensitized animals w hen given 18 h after OVA challenge. This study demonstrates that exposure t o LPS can modify the development of allergic inflammation in vivo by two in dependent mechanisms. Exposure early in the sensitization process, up to Da y 6 after exposure to allergen, prevented allergen sensitization. Exposure to LPS after allergen challenge in sensitized animals abolished the hyperre sponsiveness and modified the inflammatory cell influx characteristic of la te-phase response to allergen.