Acute respiratory response of guinea pigs to lipopolysaccharide, lipid A, and monophosphoryl lipid A from Salmonella minnesota.

Exposure to endotoxin has been associated with systemic toxicity, including pulmonary disorders such as byssinosis, as well as with beneficial biologic activities such as adjuvanticity and mitogenicity. The purified lipopolysaccharide (LPS) from endotoxin has been employed to investigate structure-activity relationships for various biologic effects. The current study was undertaken to examine the relationship between LPS structure and its ability to cause respiratory toxicity in guinea pigs after inhalation exposure. Animals were exposed to atmospheres containing 0.076 to 2.1 micrograms/m3 Salmonella minnesota LPS (S. minn. LPS), LPS from the mutant S. minn. Re595, S. minn. Re595 lipid A, and monophosphoryl S. minn. Re595 lipid A (S. minn. Re595 MPL). Each of the LPS aerosols caused increased breathing frequency (f), decreased tidal volume (VT), and airflow disturbance when measured 18 h after the 6-h inhalation exposure. The LPS preparations had equivalent toxicity, whereas the lipid A aerosol had slightly reduced toxicity. The MPL preparation did not produce this respiratory toxicity response. The results indicated that absence of the terminal phosphate group from the reducing end of the lipid A disaccharide destroyed its ability to cause the respiratory effect. These results initiate structure-activity studies of defined LPS in the lung and indicate the possibility of chemically treating endotoxins to remove adverse pulmonary effects.