Angela Mirabella

Urinary leukotriene E4 in the assessment of nocturnal asthma

BACKGROUND Urinary leukotriene E4 (LTE4) is a marker of the bodys production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest. OBJECTIVE This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE4, and the relationship between the two phenomena. METHODS Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytime FEV1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow greater than 20%). Urine was collected over 24 hours in three samples (9:00 AM to 3:00 PM; 3:00 PM to 9:00 PM; and 9:00 PM to 9:00 AM). LTE4 was measured by high-performance liquid chromatography and radioimmunoassay and expressed as nanograms per millimole of creatinine. RESULTS No significant differences between urinary LTE4 were noticed within groups A and B. Conversely, in group C urinary LTE4 at night (geometric mean with 95% confidence interval; 35.16 with 28.77-42.85) was significantly higher than that of the other samples (respectively 23.12 with 17.78-30.06, p less than 0.05; and 25.18 with 21.03-30.13, p less than 0.02); it was also significantly higher than in all the samples of other groups. A significant (p less than 0.02) linear correlation was observed between morning dip in peak expiratory flow and the log urinary LTE4 in the nocturnal sample. CONCLUSION These results indicate the role of LTs in nocturnal asthma and suggest that urinary LTE4 may be a useful marker of this condition.

IL-4 and IgE–anti-IgE modulation of 15(S)-hydroxyeicosatetraenoic acid release by mononuclear phagocytes

BACKGROUND IL-4 modulates the synthesis of IgE, the expression of CD23, and the release of 15(S)-hydroxyeicosatetraenoic (15[S]-HETE). OBJECTIVE We evaluated the release of 15(S)-HETE by IL-4-stimulated monocytes and verified whether the observed increase in 15(S)-HETE release after passive sensitization and anti-IgE challenge of IL-4-treated monocytes was secondary to an increased CD23 expression. METHODS Human monocytes were incubated for 24, 48, and 72 hours with IL-4 (10 ng/mL) with or without an IgE-anti-IgE stimulation. We evaluated CD23 expression by immunocytochemistry and 15(S)-HETE release by HPLC and RIA. To prove that the increase in 15(S)-HETE release was due to the effect of IL-4 on CD23, we performed experiments with an anti-CD23 blocking mAb. RESULTS CD23 expression and 15(S)-HETE release were significantly increased by IL-4, reaching a peak after 72 hours (P <.02). After passive sensitization with human IgE and anti-IgE challenge, IL-4-stimulated monocytes released higher amounts of 15(S)-HETE than IL-4-unstimulated monocytes (P <.02). Pretreatment with the anti-human B-cell CD23 MHM6 mAb caused a dose-dependent inhibition of 15(S)-HETE release. CONCLUSIONS This study shows that immunologic challenge of IL-4-treated, passively sensitized monocytes results in a CD23-dependent additional increase of 15(S)-HETE release, indicating the presence of a synergistic effect of IL-4 on CD23 expression and 15(S)-HETE production.

Analysis of dose-response curves in the detection of bronchial hyperreactivity.

In 12 reference subjects and 23 asthmatic patients under clinical and functional remission, dose-response curves following inhalation of nebulized carbachol solution were performed. Response was assessed both in terms of SRaw and SGaw and the best fitting mathematical function (linear, exponential, polynomial and logarithmic) was looked for. Discriminating power and day-to-day reproducibility were better when using SGaw, independently from the fitted model. For the sake of simplicity, therefore, the linear or exponential treatment of indices seem preferable.

IL-4-Induced Lipid Mediators Class Switching in Human Normal Mononuclear Phagocytes

Leukotrienes (LT) are important molecules arising from arachidonic acid, knokn to play an important role in inflammatory reactions [1]. Their synthesis is limited to a restricted number of cell involved in the inflammatory response, such as mast cells, neutrophils, eosinophils and monocyte/macrophages.