Purpose: PTX3 is a multimeric glycoprotein with a protective non redundant role against the infection caused by the fungus A. fumigatus. The activity of PTX3 against this fungal infection was originally observed in bone marrow transplanted (BMT) mice and more recently in p 47-/- mice, a murine model of the human chronic granulomatous disease (CGD). Corticosteroid treatment is one of the clinical condition that predispose to the infection with Aspergillus in patients affected by graft versus host disease (GVHD). In order to evaluate whether PTX3 could be protective towards the fungus also in condition of corticosteroid-induced immunodeficiency, we set up a rat model of invasive pulmonary aspergillosis (IPA) based on immunosuppression with cortisone acetate (CA). Methods: Immunosuppresion regime was obtained by subcutaneous injections of 150 mg/kg of CA on days -6, -4, -2, and 0, followed, the day +2, +4 and +6, by 80 mg/kg s.c.injection. On day 0 rats were intratracheally inoculated with a single administration of 5x107 conidia in 0.2 ml of saline. PTX3 was administered intraperitoneally on the day of infection and then once daily for additional three days at the doses of 0.3, 0.7, 1.5, 3 and 6 mg/kg. Results: The result of this study indicated that 1.5 mg/kg was the most effective therapeutic dose, as evaluated by survival rate and lung CFU. Because PTX3 is known to bind conidia but not hyphae of A. fumigatus, we decided to evaluate PTX3 activity following a prophylaxis schedule of administration. The protein was given for 3 days before infection and for additional 3 days post infection, at the doses of 0.15 or 1.5 mg/kg. Both these doses showed to be effective against the fungal infection with comparable activity, the dose of 1.5 mg/kg being slightly more effective than the lower tested dose. Conclusions: Taking these data all together, we conclude that PTX3 exerts a protective activity also in an animal model of IPA where immunosuppression is induced by CA. In conclusion, PTX3 appears to be a promising therapeutic option, for the potential clinical use on IPA.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)