Liposomal amphotericin B therapy reverts the immune pattern of susceptibility in acute murine paracoccidioidomycosis

Scavone, R., Nishikaku, A.S., Molina, R.F.S., Burger, E.

Author address: 

Universidade de São Paulo, SíƒO PAULO, Brazil

Abstract: 

Amphotericin B is the golden standard treatment for paracoccidioidomycosis (PCM), a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb). B10.A mice, susceptible to the infection, were treated with 5mg liposomal amphotericin B (L- AmB)/kg/day. This dose was previously determined as ideal in our experimental model and was administered by the intraperitoneal route, three times a week, starting 24 hours prior to the infection with a virulent Pb isolate. Animals submitted to therapy presented, at the 7th, 15th and 30th day post-infection, lower fungal loads and nitric oxide (NO) secretion in the spleen, epiploon, liver and lungs than control, untreated subjects. Although IFN-g, TNF-a and IL-12 levels in these organs’ supernatants were not consistently altered by the drug administration in the three time points studied, at the 30th day, treated mice showed high concentrations of IgG2a, while controls had IgG2b as the mainly isotype produced. Delayed-type hypersensitivity responses in treated mice gradually increased during the nosological course, whereas control mice developed higher responses that started earlier in the infection.These results show that L-AmB therapy elicited, in vivo, an immune profile similar to the one previously described for mice resistant to PCM. In ex vivo assays, peritoneal neutrophils and macrophages, obtained 24 hours after infection from untreated mice, had their fungicidal ability augmented when co-cultivated with different L-AmB concentrations. However, this increase was not parallel to alterations in NO, hydrogen peroxide, IFN-g, TNF-a or IL-12 levels. Financial Support: CNPq (304986/03-8) and FAPESP (04/14718-1)
2007

abstract No: 

P262

Full conference title: 

3rd Trends in Medical Mycology
    • TIMM 3rd (2011)