Evidence in man of synergistic interaction between putative mediators of acute inflammation and asthma.

The two-component hypothesis of acute inflammation postulates that the acute inflammatory response depends on both increased local blood flow and increased microvascular permeability: the validity of this concept has previously been established in animals and was tested here in man. A mixture of the mediators prostaglandin E2 and bradykinin produces a larger cutaneous wheal (volume) response than can be accounted for either by summation of the responses to the individual substances or by the slopes of their dose-response curves. This enhanced response is inhibited by noradrenaline (consistent with the vasoconstrictor property of noradrenaline) and by salbutamol (consistent with the anti-permeability property of salbutamol). These observations indicate that the two-component hypothesis of acute inflammation applies to man as well as animals; this finding is important in the evaluation of the role of putative mediators in the pathogenesis of asthma and other diseases in which inflammation plays a part.