Cyclophosphamide effect on paracoccidioidomycosis in the rat

Efecto de la ciclofosfamida en ratas con paracoccidioidomicosis

MICOLOGY

Cyclophosphamide effect on paracoccidioidomycosis in the rat

Efecto de la ciclofosfamida en ratas con paracoccidioidomicosis

J. L. Blejer; C. M. Godio; R. Negroni; M. R. Nejamkis

Department of Microbiology, School of Medicine, University of Buenos Aires, Argentina

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SUMMARY

Paracoccidioidomycosis is an endemic fungal disease widely distributed throughout Latin America. The potent immunosuppressor cyclophosphamide (CY) has been used to modulate host immune response to Paracoccidioides brasiliensis in an experimental model. Inbred male Buffalo/Sim rats weighing 250-300 g were inoculated with 5 x 10⁶P. brasiliensis cells of the yeast phase form by intracardiac route. One group of animals was treated with 20 mg/kg body weight at days +4, +5, +6, +7, +11 and +12 post-infection (pi.), while a control group was infected alone. No mortality was recorded in either group. Treated rats presented: a) a decrease in granuloma size, which contained less fungal cells; b) a lack of specific antibodies up to 35 days pi., and c) a significant increase in the footpad swelling test (DTH) against paracoccidioidin. Splenic cell transfer from CY-treated P. brasiliensis-infected donors to recipients infected alone led to a significant increase in DTH response in the latter versus untreated infected controls. Likewise, in treated infected recipients transferred with untreated infected donor spleen cells, footpad swelling proved greater than in controls. Thus, it would seem that each successive suppressor T lymphocyte subset belonging to the respective cascade may be sensitive to repeated CY doses administered up to 12 days pi.. Alternatively, such CY schedule may induce the appearance of a T cell population capable of amplifying DTH response.

Keywords: Cyclophosphamide; Delayed type hypersensitivity; Paracoccidioidomycosis; Splenocyte transfer

RESUMEN

La paracoccidioidomicosis es una enfermedad endémica fúngica ampliamente distribuida en Latino-América. La ciclofosfamida ha sido usada como potente inmunosupresor para modular la respuesta inmune, en un modelo experimental infectado con Paracoccidioides brasiliensis. Ratas machos Buffalo/Sim endocriadas de 250-300 gr. de peso, fueron inoculadas por via intracardiaca con 5.10 ⁶ células de P. brasiliensis en fase levaduriforme. Un grupo de animales fue tratado con 20 mg/kg de peso de ciclofosfamida en los dias +4, +5, +6, +7, +11 y +12 p. i. mientras que un grupo control fue infectado solaménte. No se registró mortalidad en ninguno de los grupos. Las ratas tratadas presentaron: a) una disminución en el tamaño del granuloma, el cual contenia menor cantidad de células fúngicas; b) ausencia de anticuerpos específicos hasta los 35 dias p.i. y c) un aumento significativo en el test de hinchazón de la pata (DTH) contra la paracoccidioidina. Células esplénicas provenientes de dadores infectados con P. brasiliensis fueron transferidas a receptores infectados solamente, lo que produjo un aumento significativo de la DTH en estos últimos con respecto a los controles. Asi mismo, células esplénicas de dadores infectados solamente fueron transferidas a receptores infectados y tratados mostrando tambien un aumento en la DTH con respecto a los controles.

Cada uno de los linfocitos T supresores pertenecientes a la cascada de células T parecerian ser sensibles a dosis sucesivas de ciclofosfamida hasta los 12 dias p.i.. Por otra parte, el esquema de tratamiento con ciclofosfamida podria inducir la aparición de una población de células T capaces de amplificar la respuesta DTH.

Full text available only in PDF format.

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ACKNOWLEDGEMENT

This work was supported by Grants from CONICET and from the Buenos Aires University.

Recebido para publicação em 19/10/1994

Aceito para publicação em 23/05/1995

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Correspondence to:

M. R. Nejamkis

Paraguay 2155, p. 12

(1121) Buenos Aires, Argentina

Tel. number: 541-9623290 Int. 219 Fax: [phone]

Publication Dates

• Publication in this collection
  21 Sept 2006
• Date of issue
  June 1995