Lipopolysaccharide (LPS) obtained from the bacterial species Escherchia coli has previously been shown to induce reactivity changes in guinea pig airway smooth muscle¹. As part of a continuing investigation into the mechanisms involved in the induction of hyperresponsiveness, a study has been carried out to determine if one constituent of the LPS unit is responsible for the changes involved. In vitro and in vivo experiments were carried out to compare changes between normal ‘untreated' LPS and that obtained from a preparation of LPS subject to treatment by mild alkali² to remove the lipid A (d - LPS).

In vitro, ‘normal' LPS induced a phase of smooth muscle hyperreactivity 1h post LPS exposure. However, the detoxified LPS showed no deviation from the control dose - response relationship to an applied spasmogen and hence does not cause any change in reactivity.

In vivo, a similar pattern was observed 1h post -LPS exposure. 24h after exposure to ‘normal' LPS the airway was hyporeactive to an inhaled bronchconstrictor and this persisted for a further 24h after which a return to baseline values occurred. The detoxified LPS caused no significant change compared to that seen in the saline exposed group, in vivo.

The detoxification of LPS (the removal of lipid A) is an important aspect in prevention of induction of airway hyperreactivity changes in the guinea pig.