Heme oxygenase-1 is induced in peripheral blood mononuclear cells of patients with acute pancreatitis: a potential therapeutic target.

Heme oxygenase-1 (HO-1) induction by hemin or Panhematin protects against experimental pancreatitis. As a preclinical first step toward determining whether HO-1 upregulation is a viable target in acute pancreatitis (AP) patients, we tested the hypothesis that HO-1 expression in peripheral blood mononuclear cell (PBMC) subsets of hospitalized patients with mild AP is upregulated then normalizes upon recovery and that cells from AP patients have the potential to upregulate their HO-1 ex vivo if exposed to Panhematin. PBMCs were isolated on days 1 and 3 of hospitalization from the blood of 18 AP patients, and PMBC HO-1 levels were compared with PMBCs of 15 hospitalized controls (HC) and 7 volunteer healthy controls (VC). On day 1 of hospitalization, AP patients compared with VCs had higher HO-1 expression in monocytes and neutrophils. Notably, AP monocyte HO-1 levels decreased significantly upon recovery. Panhematin induced HO-1 in ex vivo cultured AP PBMCs more readily than in HC or VC PBMCs. Furthermore, PBMCs from acutely ill AP patients on day 1 were more responsive to HO-1 induction compared with day 3 upon recovery. Similarly, mouse splenocytes had enhanced HO-1 inducibility as their pancreatitis progressed from mild to severe. In conclusion, AP leads to reversible PBMC HO-1 upregulation that is associated with clinical improvement and involves primarily monocytes. Leukocytes from AP patients or mice with AP are primed for HO-1 induction by Panhematin, which suggests that Panhematin could offer a therapeutic benefit.

Epidemiology of alcohol-related liver and pancreatic disease in the United States.

BACKGROUND: The epidemiology of acute alcoholic pancreatitis (AP), chronic alcoholic pancreatitis (CP), acute alcoholic hepatitis (AH), and chronic alcoholic hepatitis with cirrhosis (CH) alone or in combination is not well described. To better understand alcohol-related liver and pancreas effects on and associations with different ethnic groups and sexes, we analyzed the trends of AP, CP, AH, CH, AP plus AH, and CP plus CH in the United States. METHODS: We examined discharge records from the Nationwide Inpatient Sample, the largest representative sample of US hospitals. Hospital discharges, case-fatality, and sex and race contributions were calculated from patients with discharge diagnoses of AP, CP, AH, CH, AP plus AH, or CP plus CH between 1988 and 2004. RESULTS: The distribution of overall hospital discharges per 100 000 persons between 1988 and 2004 was as follows: AP, 49.2; CP, 8.1; AH, 4.5; and CH, 13.7. Overall hospital discharges per 100 000 persons for AP plus AH were 1.8; and for CP plus CH, 0.32. There were higher male to female ratios for AH and CH, and less so for AP and CP. A markedly higher frequency of AP (63.5) and CP (11.3) was seen among blacks than among whites (AP, 29.6 and CP, 5.1), Hispanics (AP, 27.1 and CP, 3.7), Asians (AP, 12.8 and CP, 1.4), and American Indians (AP, 15.5 and CP, 2.3). This higher frequency remained stable between 1994 and 2004. Overall case fatality steadily decreased in all categories, but remains highest in CH (13.6%) with similar racial distributions. CONCLUSIONS: In the United States, AP is the most common discharge diagnosis among alcohol-related liver or pancreas complications, while CH has the highest case fatality rate and male to female ratio. Blacks have the highest frequency of alcohol-related pancreatic disease.