Trends in Pharmacological Sciences
OpinionAsthma – a need for a rethink?
Section snippets
The single-mediator hypothesis
Much of our current understanding of asthma is derived from studies of patients with allergic asthma because they are often well characterized and can be made to undergo controlled airway responses to inhaled allergens, including an infiltration of eosinophils into the airways [7]. The recognition that allergen-induced airway responses were associated with airway eosinophilia led to the hypothesis that allergy and eosinophils are central to the pathogenesis of asthma [8]. This led to the
The role of eosinophils
The discovery of T helper 2 (Th2) cells and their repertoire of cytokines, in particular IL-4 and IL-5, and the recognition that allergic asthmatics often had an imbalance between Th2 and Th1 cells [14] led to the development of the Th2 hypothesis of asthma. A wide range of approaches were developed to try to switch off this cell type and/or divert the immune system to a Th1 profile, as occurs in non-allergic individuals. Two such approaches were the development of a monoclonal antibody to IL-5
A case for afferent nerves?
Much of the initial work with capsaicin was conducted in tissues from guinea-pigs. Because capsaicin-induced contraction in smooth muscle from guinea-pig airways is associated with a pronounced fall in tissue levels of sensory neuropeptides [35], most investigators attributed the effects of capsaicin to depletion of sensory neuropeptides from C-fibres. In human bronchus [36], including bronchi from subjects with asthma [37], capsaicin produces only a modest contractile response at high
Concluding remarks
The past decade has witnessed a revolution in ‘new biology’ with the ability to identify and clone receptors and ion channels almost at will. This molecular revolution is widely reported as a scientific advance that should lead to a more rapid identification of drug targets for major diseases and thus to a faster introduction of novel drugs into clinical practice. However, in asthma, like most other diseases, we are still waiting for these promised new drugs. In a recent, sobering commentary,
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Airway responsiveness in an allergic rabbit model
2011, Journal of Pharmacological and Toxicological MethodsCitation Excerpt :However, because of the lack of biological tools in the rabbit, we were unable to quantify activation status in our experiments. The release of eosinophil peroxidise or retention of this enzyme by eosinophils could be utilised as a marker of eosinophil activation (Hughes et al., 1996), although this has not been validated in our model. Nonetheless, our results are consistent with a growing number of clinical observations that eosinophils and bronchial hyperresponsiveness may be dissociated (Spina & Page, 2002).
Different mechanisms underlie the effects of acute and long-term inhibition of nitric oxide synthases in antigen-induced pulmonary eosinophil recruitment in BALB/C mice
2009, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :Selective accumulation of eosinophils into the airways has become a central concept of the asthma pathology [1,2].
Perinatal environmental tobacco smoke exposure alters the immune response and airway innervation in infant primates
2008, Journal of Allergy and Clinical ImmunologyEosinophils: Singularly destructive effector cells or purveyors of immunoregulation?
2007, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Collectively, these eosinophil-fibroblast interactions appear to be not only important contributors to local immune responses but also critical components of tissue remodeling and repair events associated with many organ/tissue–specific inflammatory events. Interactions between eosinophils and neurons have recently been recognized as events with potentially important immunoregulatory functions (see review47). For example, parasympathetic nerves have the capacity to express eotaxin, suggesting that direct recruitment of eosinophils to neurons alters neuronal plasticity, function, and survival.
Suppressive effect of verproside isolated from Pseudolysimachion longifolium on airway inflammation in a mouse model of allergic asthma
2006, International ImmunopharmacologyNovel concepts of neuropeptide-based drug therapy: Vasoactive intestinal polypeptide and its receptors
2006, European Journal of Pharmacology