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Biomedical subjects

M J Plummeridge

Publications and source records attributed to M J Plummeridge.

2 recordsLinked to original sources

Alternative agents in asthma.

Glucocorticosteroids are the backbone of asthma therapy and are administered mainly by the inhaled route. Patients with "difficult" asthma are not a single homogeneous group. Some are stable on high-dose steroid therapy but experience unacceptable side effects; others remain unstable despite receiving high doses of inhaled or oral steroids. Several different steroid-sparing and alternative agents have been tried, with varying degrees of success. Some success has been achieved with conventional immunosuppressants such as methotrexate, gold, and cyclosporin A, but these agents can be justified only in a limited range of cases. Leukotriene receptor antagonists have proved a useful addition to asthma therapy and have been shown to have a modest steroid-sparing effect. Although the existing range of alternative agents has not proved to be particularly effective, several new therapeutic agents have been developed to target specific components of the inflammatory process in asthma. These include IgE antibodies, cytokines, chemokines, and vascular adhesion molecules. Future developments might include better forms of immunotherapy and strategies targeting the remodeling of structural elements of the airways.

Anti-Asthmatic Agents↗

Reduced production of interleukin 12 by interferon gamma primed alveolar macrophages from atopic asthmatic subjects.

BACKGROUND: Asthma is characterised pathologically by an inflammatory pulmonary infiltrate rich in T helper (Th) 2 cells and eosinophils. Interleukin (IL)-12 is a heterodimeric cytokine critical for driving the development of uncommitted Th cells to express a Th 1 phenotype. Reduced pulmonary production of IL-12 may therefore play a role in the pathogenesis of asthma by contributing to the pulmonary cytokine imbalance seen in asthma. METHODS: IL-12 p70 protein levels in bronchoalveolar lavage fluid and p70 protein levels and IL-12 messenger RNA in alveolar macrophage cultures from normal and atopic asthmatic subjects were measured. RESULTS: There was a significant difference between the mean IL-12 p70 protein level in the bronchoalveolar lavage fluid from asthmatic subjects (37.5 pg/ml) and from normal subjects (131 pg/ml, p = 0.04). Alveolar macrophages from asthmatic subjects produced significantly less IL-12 protein (30 pg/ml) and messenger RNA than those from normal subjects (69.5 pg/ml, p<0.005). These differences were not caused by inhibition of IL-12 production by IL-10 nor to generalised hyporesponsiveness of asthmatic alveolar macrophages from subjects to the effects of interferon (IFN)-gamma. CONCLUSIONS: Pulmonary IL-12 production is lower in asthmatic subjects. This reduction is not the result of generalised hyporesponsiveness to IFN-gamma. Reduced IL-12 levels may contribute to the development of asthmatic pulmonary inflammation through dysregulation of Th cell development.

Adult↗