In Vivo Activity Of Interferon-  In Combination With Amphotericin B In The Treatment Of Experimental Cryptococcosis

Joly, Véronique; Saint-Julien, L; Carbon, C; Yéni, Patrick

doi:10.1093/infdis/170.5.1331

Cited by 57 publications

(34 citation statements)

References 16 publications

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“…The therapeutic potential of recombinant IFN-has been demonstrated in vivo as well as in vitro against chronic granulomatous disease [22], Cryptococcus neoformans [23], Toxoplasma gondii [21], Leishmania donovani [24] and Klebsiella pneumoniae [25]. IFN-is the principal cytokine for activating human macrophages, and it is produced in increased levels in Th1-type responses [13,15].…”

Section: Discussionmentioning

confidence: 99%

Interferon-gamma (IFN-γ) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

Johansen

Hougen²,

Rygaard³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYIn a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-). Rats were treated either before or after intratracheal challenge with P. aeruginosa embedded in alginate beads. Rats treated after challenge had a significant reduction in the severity of macroscopic lung inflammation compared with rats treated before challenge (P 0 : 004) and controls (P 0 : 003). The histopathology in controls was dominated by numerous polymorphonuclear leucocytes (PMN) ( 5 90%) surrounding the alginate beads like in CF. This could be caused by a Th2-like response. In contrast, a complete shift to a chronic-type inflammation dominated by mononuclear leucocytes ( 5 90% lymphocytes and plasma cells) and granulomas was observed in both rrIFN--treated groups of rats. This could be caused by a Th1-like response. There was no significant difference in lethality between the groups, and the antibody titres against P. aeruginosa sonicate and alginate were similar in the treated rats and controls. Since the ongoing lung tissue damage in CF patients has been shown to be caused by elastase secreted by PMN, which dominate the P. aeruginosa lung infection, our findings offer a possible new strategy of modifying the inflammatory response in CF patients.

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Section: Discussionmentioning

confidence: 99%

Interferon-gamma (IFN-γ) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

Johansen

Hougen²,

Rygaard³

et al. 1996

Clinical and Experimental Immunology

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“…These cytokines induce lymphocyte and phagocyte recruitment and activation of anti-cryptococcal delayed-type hypersensitivity responses, resulting in increased cryptococcal uptake and killing by effector phagocytes (1,6,12,18,26,27,32). Studies in mice and humans have shown some efficacy in using systemically administered recombinant Th1-type cytokines to stimulate anti-cryptococcal host responses and to enhance antifungal chemotherapy (5,15,19,20,22). Specifically, experimental studies with the Th1-type cytokine IFN-␥ have yielded some promising results as an adjunctive therapy to antifungal agents (19,29) and to significantly enhance the anti-phagocytic activity of macrophages against C. neoformans in vitro (6,12,26,34,40).…”

mentioning

confidence: 99%

“…Studies in mice and humans have shown some efficacy in using systemically administered recombinant Th1-type cytokines to stimulate anti-cryptococcal host responses and to enhance antifungal chemotherapy (5,15,19,20,22). Specifically, experimental studies with the Th1-type cytokine IFN-␥ have yielded some promising results as an adjunctive therapy to antifungal agents (19,29) and to significantly enhance the anti-phagocytic activity of macrophages against C. neoformans in vitro (6,12,26,34,40). Mucci et al have engineered a murine macrophage cell line to express IFN-␥ in an inducible manner, and this cell line was shown to enhance the anticryptococcal activity of microglial cells in a coculture system (33).…”

mentioning

confidence: 99%

“…Mucci et al have engineered a murine macrophage cell line to express IFN-␥ in an inducible manner, and this cell line was shown to enhance the anticryptococcal activity of microglial cells in a coculture system (33). Administration of recombinant IFN-␥ to C. neoformansinfected mice results in increased survival times and reduced fungal burden (21), and cytokine treatment enhances the effectiveness of the antifungal drug amphotericin B (19,29). A randomized, double-blinded, placebo-controlled clinical trial in patients with AIDS-associated cryptococcal meningitis demonstrated a trend towards more rapid sterilization of cerebrospinal fluid cultures in those treated with IFN-␥ as an adjunct to antifungals (37).…”

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confidence: 99%

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Protection against Cryptococcosis by Using a Murine Gamma Interferon-ProducingCryptococcus neoformansStrain

et al. 2007

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We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with a Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-␥). Mice given a pulmonary infection with an IFN-␥-producing C. neoformans strain were able to resolve the primary infection and demonstrated complete (100%) protection against a second pulmonary challenge with a pathogenic C. neoformans strain. Pulmonary cytokine analyses showed that Th1-type/proinflammatory cytokine and chemokine expression were significantly higher and Th2-type cytokine expression was significantly lower in mice infected with the IFN-␥-producing C. neoformans strain compared to wild-type-infected mice. This increased pulmonary Th1-type cytokine expression was also associated with significantly lower pulmonary fungal burden and significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice infected with the IFN-␥-producing C. neoformans strain compared to wild-type-infected mice. Our results demonstrate that pulmonary infection of mice with a C. neoformans strain expressing IFN-␥ results in the stimulation of local Th1-type anti-cryptococcal CMI responses and the development of protective host immunity against future pulmonary cryptococcal infections. The use of fungi engineered to produce host cytokines is a novel method to study immune responses to infection and may be useful in developing vaccine strategies in humans.

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“…To assess glucose uptake, a-methyl glucopyranoside (AMG) uptake was tested in the absence and presence of phlorizin, a potent inhibitor of the Na þ -dependent glucose co-transporter (Rabito and Ausiello, 1980). The uptake assay was performed with a-[ 14 C]AMG (NEN, Boston, MA) as described previously (Joly et al, 1990). Radioactive counts were normalized to the protein content as determined using the Coomassie Protein Assay Reagent (Pierce, Rockford, IL).…”

Section: Virus Production and Cell Transductionmentioning

confidence: 99%

Cre-mediated reversible immortalization of human renal proximal tubular epithelial cells

Kowolik

Liang

et al. 2004

Oncogene

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Primary human renal proximal tubule epithelial cells (RPTECs) are of limited use for basic research and for clinical applications due to their limited lifespan in culture. Here we used two lentivirus vectors carrying the human telomerase (hTERT) and the SV40T antigen (Tag) flanked by loxP sites to reversibly immortalize RPTECs. Transduced RPTEC clones continued to proliferate while retaining biochemical and functional characteristics of primary cells. The clones exhibited contact-inhibited, anchorage-and growth factor-dependent growth and did not form tumors in nude mice, suggesting that the cells were not transformed. Transient Cre expression in these cells led to efficient proviral deletion, upregulation of some renal specific activities, and decreased growth rates. Ultimately, the cells underwent replicative senescence, indicating intact cell cycle control. Thus, reversible immortalization allows the expansion of human RPTECs, leading to large production of RPTECs that retain most tissue-specific properties.

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In Vivo Activity Of Interferon- In Combination With Amphotericin B In The Treatment Of Experimental Cryptococcosis

Cited by 57 publications

References 16 publications

Interferon-gamma (IFN-γ) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

Interferon-gamma (IFN-γ) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

Protection against Cryptococcosis by Using a Murine Gamma Interferon-ProducingCryptococcus neoformansStrain

Cre-mediated reversible immortalization of human renal proximal tubular epithelial cells

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