Abstracts
Systemic disease by Cryptococcus neoformans (C. neoformans) is a common opportunistic infection in immunodeficient patients. Cellular immunity seems to be the most important determinant of resistance. The aim of this study was to assess the effect of recombinant rat interferon gamma (IFN-gamma) in murine cryptococcosis (Balb/c mice infected by IP route with the Rivas strain of C. neoformans), evaluating survival time, macroscopic and microscopic examination of the organs, and massive seeding of brain homogenate. IFN-gamma treatment, at a daily dose of 10,000 IU, did not modify significantly these variables when mice were challenged with a high inoculum (10(7) yeasts) and treatment was delayed to 5 days after infection (median survival 21 days in control mice vs. 23 days in IFN-treated). Another set of experiments suggested that IFN-gamma treatment, at a dose of 10,000 IU/day, begun at the moment of infection could be useful (it prolonged survival from 20 to 28 days, although the difference did not achieve statistical signification). When used simultaneously with infection by 3.5 x 10(5) yeasts, IFN-gamma at 10,000 IU/day for 15 days significantly prolonged survival of mice (p = 0.004). These results suggest that, depending on the experimental conditions, IFN-gamma can improve survival of mice infected with a lethal dose of C. neoformans.
Cryptococcosis; Interferon gamma; Experimental treatment
Se evaluó la efectividad del interferon-gamma (IFN-gamma) recombinante de rata en un modelo experimental de criptococosis desarollado en ratones Balb/C inoculados por vía intraperitoneal con la cepa Rivas de Cryptococcus neoformans (C. neoformans). Se tuvieron en cuenta el tiempo de sobrevida de los animales, el aspecto macroscópico de los órganos en la autopsia, la presencia de levaduras capsuladas en los tejidos y la siembra masiva de un homogenato de cerebro. El tratamiento con IFN-gamma, en dosis diarias de 10.000 UI, no modificó estos parámetros cuando la dosis infectante fue de 10(7) levaduras y el tratamiento se retardó 5 días post-infección (media de sobrevida de 21 vs. 23 días en los grupos de control y tratados con IFN-gamma, respectivamente). En otros experimentos observamos una prolongación del tiempo de sobrevida (aunque no significativo) de 20 a 28 días, cuando el tratamiento con 10.000 UI/día de IFN-gamma comenzó en el momento de la infección experimental. Cuando el IFN-gamma, a razón de 10.000 UI/día durante 15 días, fue administrado simultáneamente con una dosis infectante de 3,5 x 10(5) levaduras, el tiempo de sobrevida de los animales aumentó significativamente (p=0.004). Los resultados obtenidos sugieren que, dependiendo de las condiciones experimentales, IFN-gamma prolonga el tiempo de sobrevida de ratones infectados con una dosis letal de C. neoformans.
MICOLOGY
Interferon gamma increases survival in urine experimental cryptococcosis
El Interferon gamma incrementa la sobrevida de un modelo experimental murino de criptococosis
Amadeo J. Bava; Javier Afeltra; Ricardo Negroni; Roberto A. Diez
Centro de Micologia, Facultad de Medicina (UBA), Paraguay 2155 Piso 11, 1121 Buenos Aires, Argentina, and Inmunología Clínica, IO/IIHEMA
Correspondence to Correspondence to: A.J. Bava, MD c/o R. A. Diez Academia Nacional de Medicina Pacheco de Melo 3081 1425 Buenos Aires, Argentina Fax(541) 805-3415, phone (541) 805-6461, ext. 255
SUMMARY
Systemic disease by Cryptococcus neoformans (C. neoformans) is a common opportunistic infection in immunodeficient patients. Cellular immunity seems to be the most important determinant of resistance. The aim of this study was to assess the effect of recombinant rat interferon gamma (IFN-g) in murine cryptococcosis (Balb/c mice infected by IP route with the Rivas strain of C. neoformans), evaluating survival time, macroscopic and microscopic examination of the organs, and massive seeding of brain homogenate. IFN-g treatment, at a daily dose of 10,000 IU, did not modify significantly these variables when mice were challenged with a high inoculum (107 yeasts) and treatment was delayed to 5 days after infection (median survival 21 days in control mice vs. 23 days in IFN-treated). Another set of experiments suggested that IFN-g treatment, at a dose of 10,000 IU/day, begun at the moment of infection could be useful (it prolonged survival from 20 to 28 days, although the difference did not achieve statistical signification). When used simultaneously with infection by 3.5 x 105 yeasts, IFN-g at 10,000 IU/day for 15 days significantly prolonged survival of mice (p = 0.004). These results suggest that, depending on the experimental conditions, IFN-g can improve survival of mice infected with a lethal dose of C. neoformans.
Keywords: Cryptococcosis; Interferon gamma; Experimental treatment.
RESUMEN
Se evaluó la efectividad del interferon-g (IFN-g) recombinante de rata en un modelo experimental de criptococosis desarollado en ratones Balb/C inoculados por vía intraperitoneal con la cepa Rivas de Cryptococcus neoformans (C. neoformans).
Se tuvieron en cuenta el tiempo de sobrevida de los animales, el aspecto macroscópico de los órganos en la autopsia, la presencia de levaduras capsuladas en los tejidos y la siembra masiva de un homogenato de cerebro.
El tratamiento con IFN-g, en dosis diarias de 10.000 UI, no modificó estos parámetros cuando la dosis infectante fue de 107 levaduras y el tratamiento se retardó 5 días post-infección (media de sobrevida de 21 vs. 23 días en los grupos de control y tratados con IFN-g, respectivamente).
En otros experimentos observamos una prolongación del tiempo de sobrevida (aunque no significativo) de 20 a 28 días, cuando el tratamiento con 10.000 UI/día de IFN-g comenzó en el momento de la infección experimental. Cuando el IFN-g, a razón de 10.000 UI/día durante 15 días, fue administrado simultáneamente con una dosis infectante de 3,5 x 105 levaduras, el tiempo de sobrevida de los animales aumentó significativamente (p=0.004).
Los resultados obtenidos sugieren que, dependiendo de las condiciones experimentales, IFN-g prolonga el tiempo de sobrevida de ratones infectados con una dosis letal de C. neoformans.
Full text available only in PDF format.
Texto completo disponible sólo en PDF.
ACKNOWLEDGMENTS
We are indebted to Dr. E.T. Falcoff for encouraging. Roussel-Uclaf (Romainville, France) kindly provided the recombinant IFN-g used in this study.
Recebido para publicação em 27/03/1995
Aceito para publicação em 13/07/1995
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Correspondence to:
Publication Dates
-
Publication in this collection
21 Sept 2006 -
Date of issue
Oct 1995
History
-
Accepted
13 July 1995 -
Received
27 Mar 1995