Does Immunosuppressive Treatment Ameliorate Morphology Changes in Encapsulating Peritoneal Sclerosis?

Abstract

Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with ileus symptoms and irreversible sclerosis of the peritoneal membrane. Inflammation, fibrosis, and neoangiogenesis are the main features of the pathophysiology. No evidence-based therapy is currently available for EPS. In recent years, anti-inflammatory and immunosuppressive (IS) treatment modalities have become more popular. The aim of the present study was to investigate the effects of various IS treatment strategies—glucocorticosteroid (GC), azathiopurine (AZT), and cyclosporin (CsA)—on regression of EPS. We divided 52 nonuremic Wistar albino rats into six groups: Control group—2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group—2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for 3 weeks; Resting group—CG (weeks 1 – 3), plus peritoneal rest (weeks 4 – 6); Corticosteroid (GC) group—CG (weeks 1 – 3), plus 10 mg/L prednisolone in drinking water (weeks 4 – 6); AZT group—CG (weeks 1 – 3), plus 100 mg/L azathioprine in drinking water (weeks 4 – 6); and CsA group—CG (weeks 1 – 3), plus cyclosporin 7.5 mg/kg by subcutaneous injection daily (weeks 4 – 6). At the end of the study, under ketamine HCl anesthesia, the rats were humanely killed by bleeding. Parietal peritoneal samples were then taken from same location (away from the injection site) and changes of parietal peritoneum morphology were examined by a single pathologist. The CG severely disturbed parameters of peritoneal morphology, increasing peritoneal thickness, inflammatory activity, vascularity, and fibrosis score as compared with the Control group ( p < 0.05). No benefit was observed for any parameter in the Resting group as compared withthose parameters in the CG group ( p < 0.05). We observed a lower fibrosis score and less peritoneal thickness in the GC group as compared with the Resting group ( p < 0.05). No beneficial effects of AZT on peritoneal morphology were observed as compared with the effects of peritoneal rest or corticosteroid therapy. Treatment with cyclosporin resulted in more fibrosis, vascularity, and inflammation than was seen with corticosteroid therapy ( p < 0.05). Immunosuppressive therapies, especially those that are corticosteroid-based, may have therapeutic value in the management of EPS. Patients treated with cyclosporin may have a risk for developing EPS.