| First Author | Dimitrov JD | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 13 | Pages | 2682-5 |
| PubMed ID | 19890094 | Mgi Jnum | J:160804 |
| Mgi Id | MGI:4455121 | Doi | 10.1182/blood-2009-04-216408 |
| Citation | Dimitrov JD, et al. (2010) Induction of heme oxygenase-1 in factor VIII-deficient mice reduces the immune response to therapeutic factor VIII. Blood 115(13):2682-5 |
| abstractText | Replacement therapy with exogenous factor VIII (FVIII) to treat hemorrhages induces anti-FVIII inhibitory immunoglobulin G in up to 30% of patients with hemophilia A. Chronic inflammation associated with recurrent bleedings is a proposed risk factor for FVIII inhibitor development. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with potent anti-inflammatory activity. Here, we demonstrate that induction of HO-1 before FVIII administration drastically reduces the onset of the anti-FVIII humoral immune response. The protective effect was specific for HO-1 because it was reproduced on administration of the end products of HO-1 activity, carbon monoxide, and bilirubin, and prevented by the pharmacologic inhibition of HO-1 using tin mesoporphyrin IX. HO-1 induction was associated with decreased major histocompatibility complex class II expression by splenic antigen-presenting cells and reduced T-cell proliferation. Triggering the endogenous anti-inflammatory machinery before FVIII administration may represent a novel therapeutic option for preventing the development of FVIII inhibitors in hemophilia A patients. |
