Abstract
Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses. Because ferritin synthesis is stimulated by Fe2+, which is a product of heme degradation, we examined the relation between HO-1 and ferritin levels in the serum of patients with hemophagocytic syndrome (HPS), adult-onset Still's disease (ASD), and other diseases that may cause hyperferritinemia. Seven patients with HPS, 10 with ASD, 73 with other rheumatic diseases, 20 with liver diseases, 10 recipients of repeated blood transfusion because of hematological disorders, and 22 healthy volunteers were enrolled. Serum HO-1 and ferritin levels were determined by ELISA. Expression of HO-1 mRNA and protein by peripheral blood mononuclear cells (PBMCs) was determined by real-time PCR and immunocytochemical techniques, respectively. Serum levels of HO-1 were significantly higher in patients with active HPS and ASD than in the other groups (P < 0.01). HO-1 levels were not elevated in patients with other causes of hyperferritinemia but were moderately elevated in patients with dermatomyositis/polymyositis. Among patients with HPS and ASD, serum HO-1 levels correlated closely with serum ferritin levels, and the levels of both returned to normal after therapy had induced remission. Increased expression of HO-1 mRNA was confirmed in PBMCs from some patients with HPS and ASD. Hyperferritinemia correlated closely with increased serum HO-1 in patients with HPS and ASD but not other conditions, indicating that measurement of serum HO-1 and ferritin levels would be useful in the differential diagnosis of hyperferritinemia and perhaps also in monitoring disease activity in HPS and ASD.
Highlights
Heme oxygenase (HO) is an enzyme that catalyzes the conversion of heme into CO, Fe2+, and biliverdin [1,2]
The present study shows that serum Heme oxygenase-1 (HO-1) levels are significantly increased in patients with active hemophagocytic syndrome (HPS) and adult-onset Still's disease (ASD) but not in patients with hyperferritinemia due to other causes
Increased serum HO-1 levels in patients with HPS and ASD Serum HO-1 levels in patients with inflammatory rheumatic diseases were monitored by ELISA
Summary
Heme oxygenase (HO) is an enzyme that catalyzes the conversion of heme into CO, Fe2+, and biliverdin [1,2]. Evidence suggests that increased expression of HO-1 can benefit the host in a variety of pathological conditions [1,2,3,4,5]. In this context, our research team has found that HO-1 gene therapy is useful for lipopolysaccharideinduced lung injury [6], influenza viral pneumonia [7], bleomycin-induced pulmonary fibrosis [8], and chronic respiratory infection with Pseudomonas aeruginosa in mice [9]. This observation is consistent with HO-1 having a physiological effect in protecting against inflammation
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