Evaluation of the effectiveness of cyclosporine in experimental allergic rhinitis animal model

Objective: Cyclosporine is an immunosupressive molecule which inhibits synthesis of interleukin by inhibition of calcineurin in T helper cells. The objective of this study is to demonstrate whether cyclosporine has an antiallergic role in allergic rhinitis model induced in rats with ovalbumin. Study Design: Prospective, Randomized Controlled Animal Trial Material & Methods: This study was conducted on 54 Sprague Dawley female rats supplied from Bezmialem Vakıf University Medical Faculty, Experimental Application and Research Center. The experimental allergic rhinitis model was created with repeated administration of intranasal OVA following intraperitoneal injection of ovalbumin (OVA) in rats. After inducing the model, rats were treated with intranasal medication. Animals were divided into 6 groups with 9 rats in each as follows: • Group 1: negative control group (physiological saline solution (pss) sensitized + intranasal sf provocated). This group of rats was sensitized with intraperitoneal pss and administered intranasal pss. • Group 2: positive control group (ovalbumin (OVA) sensitized and provocated + intranasal pss ) This group of rats was sensitized and provocated with OVA and treated with pss. • Group 3: steroids group (OVA sensitized and provocated + intranasal corticosteroids ) This group of rats was sensitized and provocated with OVA and treated with intranasal corticosteroids. • Group 4: experimental group 1 (OVA sensitized and provocated + intranasal cyclosporine 0.05%) This group of rats was sensitized and provocated with OVA and treated with intranasal cyclosporine 0.05%. • Group 5: experimental group 2 (OVA sensitized and provocated + intranasal cyclosporine 0.10%) This group of rats was sensitized and provocated with OVA and treated with intranasal cyclosporine 0.10%. • Group 6: experimental group 3 (OVA sensitized and provocated + intranasal cyclosporine 0.20%) This group of rats was sensitized and provocated with OVA and treated with intranasal cyclosporine 0.20%. Following intranasal applications, all rats were sacrified. Intracardiac blood samples were collected to study hemogram, AST, ALT, BUN, creatinine and total bilirubin levels. Nasal and paranasal mucosae of the rats were removed, biochemical and histological examinations were performed. In the biochemical examination; tumor necrosis factor (TNF), interferon (IFN), interleukin (IL)-5, IL-13, and IL-2, IL-4, IL-17A and IgE were studied at tissue level. In histopathological analyses; loss of cilia, increase in goblet cells, vascular congestion, eosinophil infiltration and its degree were evaluated under light microscopy and scored. Results: No significant differences were found between the groups in terms of hemogram, AST, ALT, BUN, creatinine and total bilirubin levels. When the negative control group was compared with the positive control group, both histological and biochemical parameters were found to be significantly increased in the positive control group. Evaluating the groups that were treated, a significant decrease was observed in all histological values compared to the mean scores of the positive control group. No significant difference was found in inter-group comparisons of the groups administered cyclosporine. No significant difference was found in the mean histological scores between each three groups administered cyclosporine and nasal corticosteroids group which is the gold standard treatment method. Cyclosporine was histologically found to be as effective as nasal steroids. All biochemical parameters studied (IFN, IL-13, IL-2, IL-5, IL-4, TNF, IL-17 and IgE) were significantly increased in the positive control group compared to the negative control group, while these parameters were decreased in all treatment groups. This decrease did not fall to the levels of nasal corticosteroids in cyclosporine 0.05 group, but no significant difference was found between the other two cyclosporine groups (0.10 and 0.20) and corticosteroids in terms of biochemical parameters. Even these values dropped down to the levels of negative control group. Conclusion: Cyclosporine nasal drop can be safely used in allergic rhinitis animal model without producing any systemic effect. This drop is as effective as corticosteroids that are recognized as the gold standard treatment. It can be used as an alternative treatment option in intranasal treatment. Further clinical trials are needed to confirm these results.