F. Paolieri

Terfenadine and fexofenadine reduce in vitro ICAM-1 expression on human continuous cell lines.

BACKGROUND Epithelial cells and fibroblasts play an important role in allergic inflammation. Modulation of surface expression of adhesion molecules on epithelial cells by antiallergic drugs has been shown by both in vivo and in vitro studies. OBJECTIVE The aim of the study was to evaluate the effect exerted by terfenadine and fexofenadine on adhesion molecules expression (CD54/ICAM-1 and CD29) of a human continuously cultured conjunctival epithelial cell line (WK) and a fibroblast cell line (HEL). METHODS By means of flow cytometry analysis, we evaluated ICAM-1 and CD29 expression by WK and HEL epithelial cells in basal condition (at baseline) or after IFN gamma or TNF alpha stimulation in the presence or in the absence of terfenadine and fexofenadine. We also performed immunoenzymatic assays in order to evaluate soluble ICAM-1 released by WK cells and procollagen type I and III and IL6 released by HEL cells. RESULTS Terfenadine and fexofenadine significantly reduced ICAM-1 basal expression on WK cells at the concentration of 1 microg/mL and 50 microg/mL, respectively. In addition, both terfenadine and fexofenadine were able to decrease soluble ICAM-1 levels in IFN gamma-stimulated WK cells. On HEL fibroblasts, fexofenadine only was able to inhibit ICAM-1 upregulation induced by IFN gamma. Concerning the release of fibroblast products, we observed a dose-dependent decrease of spontaneous IL6 release only in the presence of fexofenadine. CONCLUSION This study shows that terfenadine and fexofenadine exert a biologic effect directly on epithelial cells and fibroblasts reducing ICAM-1 expression and partially reducing soluble ICAM-1 release.

Intercellular adhesion molecule-1 on cultured human epithelial cell lines: influence of proinflammatory cytokines

Paolieri F, Battifora M, Riccio AM, Pesce G, Canonica GW, Bagnasco M. Intercellular adhesion molecule‐1 on cultured human epithelial cell lines: influence of proinflammatory cytokines.

Topical ocular levocabastine reduces ICAM-1 expression on epithelial cells both in vivo and in vitro

Background Levocabastine is a selective topical H1 antagonist, effective in the treatment of seasonal allergic rhinitis and conjunctivitis.

Inhibition of adhesion molecules by budesonide on a human epithelial cell line (lung carcinoma)

Inhaled corticosteroids in the treatment of asthma have been shown to produce marked reductions in the number of inflammatory cells (mainly mast cells and eosinophils) and their products at bronchial level (such as cytokines). Recently, it has been demonstrated that epithelial cells express ICAM‐1/CD54 in allergic patients both during natural allergen exposure and after allergen challenge. We have previously demonstrated that deflazacort (a systemic steroid) reduces the expression of ICAM‐1 on conjunctival epithelial cells. The present study aimed to evaluate the effects exerted by budesonide on adhesion molecule expression by a human epithelial cell line (lung carcinoma: DM) and on soluble ICAM‐1. Budesonide was added at concentrations corresponding to 10−8, 10−7, and 10−6 mol/1 in cultured epithelial cells, either in the absence of any stimulus or in the presence of interferon‐gamma (IFN‐y) at 500 U/ml. After 24 h of incubation, cytofluorometric analysis was performed for ICAM‐1 and CD29/VLAP1. The 24–h supernatants of the same cultures were collected and then evaluated for soluble ICAM‐1 (sICAM‐1). The results showed that budesonide inhibits ICAM‐1 and CD29 basal expression on the cells studied (P<0.05): budesonide was effective in a dose‐dependent manner. In addition, budesonide reduced surface ICAM‐1 upregulation induced by IFN‐γ at 500 U/ml (p<0.05). Finally, cell cultures with budesonide showed decreased levels of soluble ICAM‐1 in basal condition, but not after IFN‐γ stimulation.

Antiallergic activity of topical lodoxamide on in vivo and in vitro models

Lodoxamide is an antiallergic drug acting as a mast‐cell stabilizer, which is effective in the treatment of allergic conjunctivitis. The study aimed to evaluate the effect of lodoxamide eye‐drops on the inflammatory early‐phase reaction (EPR) changes induced by allergen‐specific conjunctival challenge (ASCC). This was a cross‐over, double‐blind, placebo‐controlled, randomized study, including 10 outpatients suffering from allergic rhinoconjunctivitis due to Parietaria judaica. Patients received one drop of lodoxamide tromethamine 0.1% or placebo 30 min before each ASCC. Clinical evaluation and cytologic assessment were done at baseline and 30 min after each ASCC. Lodoxamide induced a reduction in total symptom score and hyperemia during the EPR (P < 0.05). Lacrimation, itching/ burning, and eyelid swelling were only slightly (nonsignificantly) reduced. Lodoxamide induced a reduction in the total number of inflammatory cells and neutrophils during the EPR (P < 0.02). Eosinophil and lymphocyte number and ICAM‐1 expression showed only a slight, not statistically significant decrease. Placebo did not affect the studied parameters. Lodoxamide reduced early clinical events and cellular changes after ASCC consistently with its activity as mast‐cell stabilizer. Moreover, lodoxamide was able to downregulate in vitro ICAM‐1 expression on the continuously cultured, differentiated conjunctival cell line WK. This was shown both in basal conditions (P < 0.05) and upon interferon‐gamma stimulation (P < 0.03), although at high concentration.

Co-Stimulatory Molecules in Graves’ Disease

Most immune responses depend on the activation of T cells. This class of lymphocytes consists of functionally and phenotypically distinct populations, the best characterized of which are helper and cytotoxic T cells. CD4+ helper T cells can be divided into two subtypes. Type 1 helper T cells (Th1) mainly synthesize interferon-γ and interleukin (IL)-2; type 2 helper T cells (Th2) principally secrete IL-1, IL-5, and IL-10 (1). The pathogenesis and outcome of certain diseases appears to be strongly influenced by the type of helper T cells involved. For example in leishmaniasis the development of a response polarized toward Th1 is important for a successful immune defence, but a response polarized toward Th2 is detrimental as demonstrated in an animal model (2).