Cyclophosphamide effect on coccidioidomycosis in the rat Efecto de la ciclofosfamida en la infección por Coccidioides immitis en la rata

• Published in: Revista do Instituto de Medicina Tropical de São Paulo
• Main Authors: Mirta C. Remesar, Jorgelina L. Blejer, Ricardo Negroni, Marta R. Nejamkis
• Format: Article in Journal/Newspaper
• Language: English
• Published: Universidade de São Paulo (USP) 1989
• Subjects: Cyclophosphamide; Coccidioidomycosis; Immunosuppression; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Acosta; Arctic; Droga; Rata
• Online Access: https://doi.org/10.1590/S0036-46651989000600009; https://doaj.org/article/91010b2f476a47d8a92218cb96cc5977

Coccidioidomycosis is a systemic mycosis, endemic in arid areas of the American continent. The rat was employed as an experimental host, since it had been shown to reproduce human lesions and present a chronic course of disease with granulomas mainly restricted to lungs. Given the influence of immunosuppressive therapy on the clinical course of human coccidioidomycosis, we studied the effect of cyclophosphamide (CY) in the experimental rat model. Accordingly, animals were inoculated with 400 Coccidioides immitis arthroconidia of the Acosta strain, by intracardiacal route. As single CY doses failed to alter the course of disease, three schedules were used: A) 4 daily doses of 20 mg/kg each, prior to C. immitis inoculation; B) 4 similar daily doses after infection; and C); 6 doses of 20 mg/kg each, given from day +1 to +4, then on days +8 and +9, post infection (pi), taking day 0 as the time of fungal inoculation. The first two schedules inhibited antibody formation up to day 28 pi, without modifying cellular response to coccidioidin as measured by foodpad swelling. Initially, there was greater fungal spread than in controls receiving C. immitis alone, which proved self-limiting in the latter. In contrast, schedule C led to 559r mortality, with both humoral and cellular response abrogation, accompanied by extensive C. immitis dissemination. Histology disclosed significant alterations, such as the persistence of primary infection sporangia, corresponding to the acute stage of coccidioidomycosis in the absence of granuloma development. Therefore, the observed depression in cellular immunity seems responsible for the lack of inflammatory reaction capable of restricting sporangia proliferation in tissues which, in turn, enhances pathogen spread and mortality rate. El propósito de este trabajo fue estudiar el efecto de la inmunosupresión causada por la droga ciclofosfamida (CY) sobre la infección de la rata con Coccidioides immitis por vía intracardíaca. Este huésped fue empleado como modelo experimental, ya que ...