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Cyclophosphamide effect on coccidioidomycosis in the rat
Revista Do Instituto De Medicina Tropical De Sao Paulo
|November 1, 1989
Summary
Cyclophosphamide (CY) treatment in a rat model of coccidioidomycosis worsened disease by suppressing immune responses. This immunosuppression led to increased fungal spread and mortality, highlighting the importance of cellular immunity in controlling this fungal infection.
Area of Science:
- Medical Mycology
- Immunology
- Infectious Diseases
Background:
- Coccidioidomycosis is a fungal infection endemic to arid regions of the Americas.
- Rats serve as a model for human coccidioidomycosis, displaying chronic disease and granuloma formation.
- Immunosuppressive therapy significantly impacts coccidioidomycosis progression in humans.
Purpose of the Study:
- To investigate the effect of cyclophosphamide (CY), an immunosuppressive agent, on experimental coccidioidomycosis in rats.
- To determine how different CY dosing schedules influence the course of Coccidioides immitis infection.
Main Methods:
- Rats were inoculated with Coccidioides immitis arthroconidia.
- Three cyclophosphamide (CY) treatment schedules were administered: pre-infection, early post-infection, and a prolonged post-infection schedule.
- Humoral and cellular immune responses were assessed, alongside fungal dissemination and mortality rates.
Main Results:
- Single CY doses did not alter disease course.
- Schedules A and B (early CY) suppressed antibody formation but not cellular responses, initially increasing fungal spread.
- Schedule C (prolonged CY) resulted in 55% mortality, abrogated immune responses, extensive fungal dissemination, and lack of granuloma formation.
Conclusions:
- Cyclophosphamide-induced immunosuppression, particularly affecting cellular immunity, exacerbates coccidioidomycosis in rats.
- The lack of inflammatory response allows for uncontrolled fungal proliferation and increased mortality.
- This model underscores the critical role of intact cellular immunity in limiting Coccidioides immitis infection.