Suppression of peritoneal thickening by histamine in a mouse model of peritoneal scraping

Background: Inflammatory reactions play an important role in peritoneal sclerosis in patients on peritoneal dialysis. Since histamine affects inflammatory reactions and immune responses, we investigated effects of intraperitoneal administration of histamine on peritonitis induced by mechanical scraping in mice. Methods: After anesthesia, the right peritoneum was scraped 90 times over 1 min, and bilateral peritonea were observed by light microscopy after 7 days. Results: Thickness of the peritoneal membrane on the right side was 174 ± 77 µm (mean ± SD, n = 8), while that on the left side was 24 ± 19 µm. Intraperitoneal administration of histamine (0.3 or 1.0 mmol/L, 0.5 mL each) twice daily for 7 days after scraping decreased thickness of the right peritoneum to 42 and 43 % of that in saline-injected animals, respectively (P < 0.01), although histamine (0.1 mmol/L) did not affect it. Promethazine (5 nmol, twice daily for 7 days), a histamine H₁ receptor antagonist, abolished the amelioration caused by histamine (1.0 mmol/L). Neither ranitidine (15 nmol), a histamine H₂ receptor antagonist, nor thioperamide (7.5 nmol), a histamine H₃/H₄ receptor antagonist, affected the outcome in histamine-treated mice. Conclusion: These findings indicate that histamine H₁ action partly prevents the development of peritoneal fibrosis caused by mechanical scraping.