Expression of caspase 1 and histomorphology of lung after cladribine treatment.

BACKGROUND: Cladribine is a useful immunosuppressive drug for the treatment of autoimmune diseases, leukemias and multiple sclerosis (MS). Despite the drug having low toxicity, side effects have been reported connected with myelosuppression, neutropenia and severe anemia.

OBJECTIVES: The objective of this study was to investigate the influence of cladribine on lung pathomorphology and the expression of caspase 1 using immunohistochemistry method.

MATERIAL AND METHODS: The study was conducted on Wistar rats, which were divided into: one control group (C) and one experimental group (E). In group C, the rats were given a 0.9% NaCl solution by way of a subcutaneous injection, at the same dose as the dose of drug used in the experiment. In group E, the animals received cladribine at a dose of 0.07 mg/kg/24 h by way of a subcutaneous injection. The animals were decapitated 24 h following the last dose. To detect collagen deposition, we utilized Masson's trichrome staining. To evaluate the intensity of the inflammatory process in the lung, an immunohistochemistry reaction was carried out with the use of caspase 1.

RESULTS: In group E, we observed an increase in the thickness of space between the alveoli. A statistically significant (p < 0.017243) difference between the thicknesses of the interalveolar septum was seen between the research groups. In E group, we observed regions with collagen deposition, alveolar epithelial cell hyperplasia, hyperemia and inflammatory cell infiltration. Caspase 1 activity was higher in the group E. The immunohistochemical reaction with caspase 1 was positive in 49% of all the interalveolar cells in the group E; however, in group C about 13% of the interalveolar cell showed positive immunohistochemistry (IHC) response.

CONCLUSIONS: Cladribine-based therapy might have negative influence on lung morphology. The interstitial changes in the lung tissue suggest that cladribine is a drug that may be the cause of drug-induced lung disease and may lead to several respiratory disorders.