EJMS

Abstract

Introduction: Sirolimus (Rapamune) is a new immunosuppressant that has been approved by the US -FDA and is gaining popularity. Recently, reports of interstitial lung disease in patients treated with sirolimus have been reported. It is unclear whether sirolimus is directly related to the occurrence of such lung toxicity or whether other factors might be involved. Aim of the Work: This study was carried out to demonstrate the effect of sirolimus on the lung structure and the possibility of recovery after its withdrawal. Materials and Methods: Thirty adult male albino rats were used and were divided into three main groups (10 animals each); a control group, sirolimus treated group which received 1 mg/kg body weight of sirolimus orally once daily for 4 weeks, and the third group received the same dose of sirolimus as the second group then the drug was stopped for 4 weeks. Lung specimens were processed for histological study by light microscopy and stained immunohistochemically by Cox-2 antibody for detection of apoptotic cells. Results: In sirolimus treated rats the lung showed significant decrease in the thickness of the inter-alveolar septa of the treated group with mononuclear cellular infiltration associated with alveolar damage and many collapsed alveoli. Orcine stained sections showed a decrease in elastic fibers and Mallory trichrome showed increase in the collagen content of the inter-aleveolar septa when compared with the control group. Significant increase in Cyclooxygenease-2 (Cox-2) positive alveolar cells was detected. After stoppage of sirolimus treatment, these changes in lung structure showed partial recovery with persistence of lung fibrosis suggesting that the lung toxicity of sirolimus was partially reversible. Conclusion: Sirolimus could induce alveolar damage and pulmonary fibrosis and it is recommended that patients under sirolimus treatment should be regularly examined for early detection of interstitial pneumonitis.