Characterizing the Effect of Pentamidine Isethionate on the Immune System Using Mouse Splenocytes as an Experimental Model

Abstract

Evaluating immunomodulating effects is currently a fundamental parameter when designing pharmaceutical products. Rather than wait for the appearance of immunotoxic effects in patients, pre-clinical assays that characterize these potential events in experimental models not only can facilitate the understanding of how these phenomena arise, but sometimes reveal findings that can lead to modifications in currently-accepted methodologies used for estimating the pre-clinical assay predictive risk values. Pentamidine isethionate, a drug used as a second option in treating leishmaniasis, has been repeatedly shown in animals and humans to exert a toxicity at the renal, cardiac and hepatic level; however, its immunotoxic effect have not been as fully evaluated. The potential immunomodulatory effects of pentamidine on splenocytes from two species of mice (BALB/c and ICR) were evaluated ex vivo in this study. The results here indicated that there were significant differences in subpopulation profiles between the strains even before treatment with the drug, with the variances most apparent regarding the relative percentages of CD8 + and CD19 + cells in splenocyte preparations. The data also showed that the drug preferentially induced toxicity in BALB/c mice CD8+ and CD19 + cells more so than in their ICR Received 21 May 2007; Accepted 28 August 2007. We would like to thank the Pharmacy Department from the Universidad Nacional de Colombia and the Instituto Nacional de Salud (INS) for donating the mice used in the study. We would also like to thank Jason Garry for translating the manuscript. This research was performed with support from the Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología "Francisco José de Caldas" "Colciencias" Contract #060/2006. We would also like to thank Becton Dickinson Colombia and Equimed Ltda. for supplying some of the materials and reagents needed for carrying out the project. The authors have no conflicts of interest that are directly relevant to the content of this study. Authors Plaza and Marino are also affiliated with the Biology Department, Universidad Nacional de Colombia, Bogota, Columbia; Authors Marino and Delgado have dual affiliation with Pharmacy Department, Universidad Nacional de Columbia, Bogota, and Author Plaza is also affiliated with the Fundacion Instituto de Immunologia de Colombia, Bogota.Abbreviations:7AAD, 7-amino-actinomycin D; ISI, inverse stimulation indices; MFI, mean fluorescence intensity.Address correspondence to Dr. Gabriela Delgado, Carrera 50 No. 45-03, Edificio 450, Departamento de Farmacia, Oficina 206, Ciudad Universitaria, Bogota D.C., Colombia; e-mail: lgdelgadom@ unal.edu.co counterparts. Conversely, the ICR cells seemed to be more susceptible to drug-induced spontaneous blastogenesis than the cells from BALB/c hosts. The differential results seen here confirm that: any potential immunomodulatory effect of a drug should be studied in at least two different mouse strains during an evaluation of overall toxicologic potential; and, there shou...

Antileishmanial and immunomodulatory activity of Xylopia discreta

“…According to these studies, MCP‐1 would be an important healing and resistance mediator in cases of cutaneous and visceral leishmaniasis. Taking into account the previous reports and our results, it would be relevant to analyse the immunotoxic/immunomodulatory effect of substances in this kind of infections (30) because studying only their antiparasitic effect leaves aside the potential action that these substances might have on the immune system, which is known to be critical for properly controlling infection by intracellular obligate parasites such as Leishmania . At a technical level, we suggest that the methodological approach followed in this study is fast, cost‐effective and reproducible for screening potential antileishmanicidal or immunomodulatory substances at a large scale.…”