Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats.

Abstract

We determined the effect of cyclosporine A (CSA) on airway reactivity and remodeling after chronic antigen challenge in Ascaris suum (AA)-sensitized cats. CSA efficacy was demonstrated by inhibition of interleukin-2 (IL-2) production from phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear (PBMN) cells. Twenty-four hours after the first AA exposure, cats not receiving cyclosporine (CsA-) demonstrated airway hyperresponsiveness (AHR) to acetycholine (approximately 1.0 log increase in PD200 versus baseline; p < 0.01), and a 13-fold increase in eosinophils in bronchoalveolar lavage fluid (BALF) (p < 0.01). AHR persisted (approximately 1.5 log increase in PD200 p < 0.001 versus baseline), and BALF eosinophilia was unchanged in CsA-cats 72 h after final AA challenge. The percent of normodense BALF eosinophils also decreased substantially in CsA-cats (p < 0.05). Necropsy specimens from CsA-cats demonstrated: (1) increased smooth-muscle thickness; (2) goblet cell and submucosal gland hypertrophy and hyperplasia; and (3) epithelial erosion with eosinophilic infiltration. There was no significant change in AHR, BALF, eosinophilia, or histology after chronic AA challenge in Csa-treated cats. These data suggest that CsA inhibits products of immune cells necessary for the development of AHR, airway inflammation, and airway wall remodeling caused by immune-sensitization in this model of atopic asthma.

An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema

“…To detect Th1 polarization, we assessed lung lymphocytes for expression of CCR5 (a receptor for several Th1 chemokines) and CXCR3 (the receptor for IP-10, I-TAC, and MIG). We screened for the presence of Th2 cells by assessing T cell expression of CCR4—a receptor for eotaxin/CCL11, macrophage chemoattractant protein 3 (CCL7), and thymus- and activation-regulated chemokine (CCL17) [40,41]—and CCR3, a receptor for eotaxin and related chemokines. Flow cytometry revealed very low expression of CCR3 and CCR4 (1%–3%) in control ( n = 10) and emphysema ( n = 18) groups, and did not discriminate between these populations (Figure 1A and 1B; data not shown).…”

Feline Bronchial Disease/Asthma

“…[1][2][3][4][5] Clinical signs range from intermittent cough to severe respiratory distress; these are attributable to airway obstruction caused by bronchial inflammation, with subsequent smooth muscle constriction, epithelial edema, and mucous gland hypertrophy and hyperactivity. However, considerable research has been completed on these syndromes in recent decades, and the disease in cats has been better characterized by the use of an experimental model of antigen-induced inflammatory bronchial disease.…”

“…5 Reports have not been published to corroborate this response in the clinical setting; however, it is possible that blockade of serotonin might alleviate clinical signs in vivo. 3 Cyclosporine therapy might be indicated for those cats with especially severe or end-stage bronchial disease, or for those that are unresponsive to more standard medical management, although no clinical trials have been carried out to date. Potential side effects of cyproheptadine are related to its other antiserotonin effects, and include lethargy and increased appetite.…”

Functional response to inhaled salbutamol and/or ipratropium bromide in Ascaris suum-sensitised cats with allergen-induced bronchospasms

“…Historically, cyclosporine A, an effective inhibitor of T-cell activation, has been the first drug to be shown to prevent bronchial hyperreactivity and cytological/morphological alterations in the airways of AS-sensitised and chronically challenged cats (Padrid et al, 1996). Potent immunosuppressive effects, requirement for continued monitoring and exorbitant expenses have precluded cyclosporine A from the routine management of feline asthma and emphasise the need to widen therapeutic options.…”