Changes in beta-adrenergic responses as a consequence of infection with micro-organisms

The B. pertussis model of atopy as proposed by Szentivanyi in 1968 has been a starting point for much research involving the pathogenesis of COLD. Moreover, it supplied more insight into the pharmaco-therapeutic approach toward this group of diseases. In this review, it is shown that products of bacteria considered to be a constituent of the normal flora of the human upper respiratory tract, such as H. influenzae, elicit changes in adrenoceptor responsiveness which are compatible with an enhanced tendency toward bronchoconstriction. One of the features of human atopy is enhanced mediator release after appropriate stimuli resulting in bronchoconstriction. This phenomenon can be mimicked in an animal model, the H. influenzae-vaccinated rat or guinea pig; enhanced histamine synthesis and release are found in vivo as well as in vitro. The effects point in the direction of a beta-adrenergic defect which is not only demonstrable in biochemical but also in physiologically oriented parameters. Pulmonary smooth muscle tissue appears to be less responsive to beta-adrenergic agonists and has an enhanced tendency to contract. The view that these changes are indeed the reflection of changes in adrenoceptor systems has been investigated in guinea pigs and rats. In both species impairment of beta-adrenergic systems together with a reduction in the number of beta 2-adrenoceptors was found after vaccination. Also the involvement of other factors, e.g., catecholamines, has been demonstrated. Comparable changes occur within the pulmonary adrenoceptor populations of COLD patients, suggesting disturbed homeostasis in the autonomic nervous system, possibly leading to bronchoconstriction. The question whether a bacterial factor is important in these changes and might induce, sustain or enhance the effects of other factors or even have a role in the pathogenesis of COLD is discussed in this review.