Effect of poloxamer CRL-1072 on drug uptake and nitric-oxide-mediated killing of Mycobacterium avium by macrophages

Jagannath, Chinnaswamy; Sepulveda, Eliud; Actor, Jeffrey K.; Luxem, Franz; Emanuele, Martin; Hunter, Robert L.

doi:10.1016/s0162-3109(00)00203-4

Cited by 8 publications

(5 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33 However, others reported that the intracellular growth of NO-sensitive MAC strains was signi®cantly suppressed by NO generated by IFNc-stimulated macrophages while that of NO-resistant MAC strains was not. 34,35 Control of MAC infection requires the presence of activated CD4 + T cells, especially Th1 cells, which produce an array of cytokines, including IFN-c, involved in activating macrophage bactericidal activity. Studies involving IFN-c gene and IFN-c receptor gene knockout mice showed that IFN-c, produced by activated Th1 cells and perhaps NK cells, played an essential role in protective cellular immunity against mycobacteria.…”

Section: Discussionmentioning

confidence: 52%

“…MAC was more effectively cleared in mice genetically deficient in the inducible NO synthase (iNOS −/− ) gene than in wild‐type mice, suggesting that NO is not involved in the anti‐mycobacterial mechanisms of MAC‐infected macrophages 33 . However, others reported that the intracellular growth of NO‐sensitive MAC strains was significantly suppressed by NO generated by IFNγ‐stimulated macrophages while that of NO‐resistant MAC strains was not 34,35 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin‐18

2001

View full text Add to dashboard Cite

SUMMARYInterferon-gamma (IFN-c) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) was known to strongly induce IFN-c production by T cells and natural killer (NK) cells. In order to determine whether injection with DNA encoding IL-18 can stimulate the resistance to Mycobacterium avium complex (MAC) infection, the mature IL-18 cDNA with k leader sequence was cloned under control of the cytomegalovirus (CMV) promoter (TcCMVIL-18) and its effect on MAC infection was investigated in genetically susceptible BALB/c mice. Injection with the TcCMVIL-18 DNA during intranasal infection with MAC resulted in a signi®cant decrease in bacterial load of lung during the entire 8-week observation period, while injection with the TcCMV control DNA did not. Lung cells in mice injected with the TcCMVIL-18 DNA showed persistent production of IFN-c throughout the 8-week period. Furthermore, immunization with the TcCMVIL-18 DNA induced and maintained signi®cantly higher levels of cytotoxic activity and nitric oxide production by lung cells than immunization with the TcCMV control vector. This work suggests that IL-18 DNA vaccination may be useful in the immunotherapeutic or immunoprotection approaches of infections by intracellular parasites such as mycobacteria.

show abstract

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin‐18

2001

View full text Add to dashboard Cite

show abstract

“…The mechanisms of action of CRL-1072 are poorly understood. The surfactant induces production of nitric oxide in cultured human macrophages, leading to improved clearance of MAC (125). In addition, CRL-1072 induces production of IL-8 in human macrophages, a chemotactic factor which attracts neutrophils and T cells to the site of infection (126).…”

Section: Hdts With Unknown or Poorly Understood Mechanisms Of Action Poloxamer Crl-1072mentioning

confidence: 99%

The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex

2021

View full text Add to dashboard Cite

Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.

show abstract

“…The possibility to use Pluronic block copolymers to overcome resistance to certain antifungal agents has been also demonstrated. [173][174][175][176] Overall one should expect further scientific developments using polymer micelle delivery systems for treatment of fungal infection.…”

Section: Formulations Of Antifungal Agentsmentioning

confidence: 99%