Steroid and Antihistamines Modulate Rantes Release in Cultured Peripheral Blood Mononuclear Cells of Atopic Patients

Abstract

RANTES plays a crucial role in cell recruitment in allergic inflammation. We investigated the pharmacological modulation of RANTES release in cultured peripheral blood mononuclear cells obtained from allergic patients with active asthma. Chemokine production was assessed before and after 15 day treatment with histamine-I receptor antagonists (Loratadine or Cetirizine) and a steroid (Deflazacort), both in unstimulated and PHA-stimulated cell cultures. Results were compared with those obtained from placebo-treated patients. During the treatment period, patients recorded morning and evening peak expiratory flow (PEF) by mini-Wright.PEF absolute values and diurnal variability significantly improved respect to the pre-treatment in steroid-treated patients, in comparison to the placebo and antihistamine-treated groups (p<O.OOI and 0.01, respectively). PEF diurnal variability in the antihistamine-treated group were lower than placebo-treated group without statistical significance (p=0.06). No differences could be found in RANTES levels in supernatants of all cultures between the two antihistamines. RANTES release significantly decreased in supernatants of all cell cultures from steroid (p<O.OI) and antihistamine (p=0.03 and 0.04) groups after treatments, compared to the basal values; whereas it increased slightly in controls. Co-variance analysis on RANTES levels, adjusting for pre-treatment values, showed a significant reduction of RANTES release by PHA-stimulated PBMCs from steroid (p=0.003) and anti-histamine (p=0.03) groups, with respect to the placebo group. The same statistical tool applied between the steroid and the antihistamine groups showed, after therapy, the lowest levels of RANTES to be associated with steroid treatment (p=0.005). The study shows that steroid is the most effective drug in modulating RANTES release from PBMCs. However, antihistamines, which are able to reduce cell recruitment due to chemokine release, avoiding important side effects, may be useful in long term therapy in controlling and preventing allergic inflammation.RANTES is a member of the C-C chemokine family showing a strong chemotactic activity for lymphocytes, eosinophils, mast cells, and monocytes/macrophages (1).Our previous studies reported that RANTES is able to induce 5-hydroxytryptamine (5-HT) and histamine release from rat mast cells and basophils (2,3). RANTES is produced in immediate allergic reactions and delayed-type hypersensitivity reactions; it may interact with both Thl and Th2-derived cytokines for modulating the inflammatory reaction. It contributes to inflammatory cell recruitment (4,5), particularly of eosinophils (6), memory T cells and monocytes (7). Some

Effectiveness of Montelukast versus Budesonide on Quality of Life and Bronchial Reactivity in Subjects with Mild-Persistent Asthma

“…Our data point out the importance of intervening in asthmatic disease, above all in the earlier phases of its clinical manifestation, when a variety of mechanisms play a role in the development of bronchial inflammation (16)(17)(18)(19)(20)(21)(22)(23)(24)(25), involving many cells and cytokines, and when remodeling phenomena are not so advanced to determine persistent obstruction. In this early phase intervention with long-term anti-inflammatory medications, such as anti-leukotrienes, the consequences of remodeling on the bronchial wall, and thus persistent bronchial obstruction, bronchial hyper-responsiveness, decline of lung function may be avoided (26).…”

Secretion of RANTES (CCL5) and interleukin‐10 from mesenteric adipose tissue and from creeping fat in Crohn’s disease: Regulation by steroid treatment

“…Therefore, one would expect an upregulation of RANTES secretion rather than a downregulation by steroids. As shown extensively in the literature, steroid treatment usually reduces RANTES secretion from mononuclear cells in the context of atopic and chronic inflammatory diseases 27,28 . However, steroid effects on adipose tissue mononuclear cells might differ completely from those observed on soluble immune cells.…”

Association between RANTES promoter polymorphism −401A and enhanced RANTES production in atopic dermatitis patients

“…Enhanced RANTES production has been found in serum and skin lesions of AD patients, while treatment with steroids has the important effect of lowering the expression level of RANTES in atopic patients [1][2][3]. These reports suggest a potential role of RANTES in AD, and that the alteration of RANTES gene expression might be involved in the development and progression of AD.…”