No abstract

Vascular endothelial growth factor (VEGF) and its endothelial cell receptors (VEGFR) have been shown to be involved in the pathogenesis of the contact hypersensitivity (CHS) reaction. Previous studies have demonstrated that anti-VEGFR-2 antibody significantly suppresses the elicitation phase of CHS but does not affect the induction phase. PTK787/ZK 222584 (1-[4-chloroanilino]-4-[4-pyridylmethyl] phthalazine succinate; PTK/ZK) is a potent inhibitor of VEGFR tyrosine kinases. To test the effect of PTK/ZK on the induction and elicitation phases of CHS separately, we used an established method of CHS assay-sensitization and challenge in BALB/c mice. Either 50 mg/kg/day PTK/ZK or vehicle serving as a control was administered orally in the induction or elicitation phases separately. In the afferent phase, flow cytometry of skin-draining lymph node cells revealed that the migration of Langerhans cells was suppressed in the mice treated with PTK/ZK at sensitization. The degrees of ear swelling at 24 and 48 h were significantly diminished in mice treated with PTK/ZK at sensitization (P < 0.05). In the efferent phase, the degrees of ear swelling at 24 h (P < 0.01) and 48 h (P < 0.05), ear blood flow at 24 and 48 h (P < 0.01), and production of VEGF in the epidermis at 24 h (P < 0.05) were significantly suppressed in mice treated with PTK/ZK at elicitation. These findings and previous demonstrations suggest that both VEGF R-1 and VEGF R-2 are needed during the induction phase, and that VEGFR-2 has a pivotal role in the elicitation phase of the CHS reaction.

Clinical Pharmacology & Therapeutics (2003) 73, P22–P22; doi:

No abstract

Objective: In general, antiallergic drugs, steroids, and autonomic drugs are administered for patients with allergic diseases, but the chronic administration of these medicines may occasionally induce side effects. As such, several complementary and alternative medicine (CAM) are used, even though their effectiveness has not been established by a significant amount of evidence. Health food, herbal medicines, herbal tea, and aromatherapy, etc., are used for the treatment of allergic rhinitis (AR) as CAM. Rosmarinic acid is a type of polyphenol, and is reported to have antiallergic, antioxydative and anti-inflammatory properties. Rosmarinic acid is included in Perilla Herbs, which are used in health foods and herbal medicines (Kampo medicines), Rosemary and Lemon balm, which are used as herbal teas and essential oils of aromatherapy. This study was performed to evaluate the effect of rosmarinic acid on AR using AR model rats.Methods: Six-week-old male Sprague-Dawley rats were sensitized with toluene 2,4-diisocyanate (TDI) to induce AR. Rosmarinic acid (1 mg/kg i.p. or 3 mg/kg i.p.) is administrated for 21 days. On day 22, the symptom of nasal allergy was evaluated by counting the number of sneezes within 10 minutes. Substance P (SP), calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) in the nasal lavage fluids were also measured.Result: SP and CGRP take part in the exacerbation of rhinitis symptoms, and are secreted from the nerve ending following nerve stimulation by chemical mediators such as histamine. The administration of Rosmarinic acid had no effect on NGF, but significantly suppressed increases of sneezes, SP and CGRP dose-relatedly. Conclusion: Rosmarinic acid could control the symptom of nasal allergy, and one of the mechanisms was suppressing of the secretion of SP and CGRP.