The<i>in vitro</i>and<i>in vivo</i>effects of clofazimine on the motility of neutrophils and transformation of lymphocytes from normal individuals

Gärtner, E.; Rensburg, C E Van; Imkamp, Florian

doi:10.5935/0305-7518.19820010

Cited by 8 publications

(6 citation statements)

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“…Clofazimine, which is used against leprosy, already has two distinct antibacterial targets, guanine bases and phospholipase A2 . In addition to these activities, it also reduces neutrophil mobility, which is beneficial for treating patients with a type 2 lepra reaction characterized by strong inflammation. , The range of antibiotics with immunomodulatory and anti-inflammatory effects and the detailed use of these compounds have been thoroughly reviewed before ,− and should not be described here in more detail. However, it should be noted that daptomycin has been implicated to have immunomodulatory effects as well .…”

Section: Part 1: Multitarget Compoundsmentioning

confidence: 99%

Multitarget Approaches against Multiresistant Superbugs

2020

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Despite efforts to develop new antibiotics, antibacterial resistance still develops too fast for drug discovery to keep pace. Often, resistance against a new drug develops even before it reaches the market. This continued resistance crisis has demonstrated that resistance to antibiotics with single protein targets develops too rapidly to be sustainable. Most successful long-established antibiotics target more than one molecule or possess targets, which are encoded by multiple genes. This realization has motivated a change in antibiotic development toward drug candidates with multiple targets. Some mechanisms of action presuppose multiple targets or at least multiple effects, such as targeting the cytoplasmic membrane or the carrier molecule bactoprenol phosphate and are therefore particularly promising. Moreover, combination therapy approaches are being developed to break antibiotic resistance or to sensitize bacteria to antibiotic action. In this Review, we provide an overview of antibacterial multitarget approaches and the mechanisms behind them.

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Section: Part 1: Multitarget Compoundsmentioning

confidence: 99%

Multitarget Approaches against Multiresistant Superbugs

2020

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“…also known as lamprene or B663, is an effective anti-leprosy agent [13.14,37] with antiinflammatory and immunosuppressive properties [38][39][40] that stimulates the phagocytic and microbicidal activities [15] of human and murine phagocytes [38][39][40] by potentiating thc activity of lysosomal enzymes [16,41]. The increased intracellular killing abiHty of phagocytes in the presence of clofazimine has been suggested to be due to its priming effects on phagocytes [17].…”

Section: Discussionmentioning

confidence: 99%

HLA expression in hepatocellular carcinoma cell lines

Wadee

Paterson

Coplan

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThe present study undertook to investigate the biological significance of human leucocyte antigen expression in hepatoceilular carcinoma and to elucidate lhc role of potential modulating agents on human leucocyte antigen expression. These studies used several hepatic tumour-derived cell lines as in vitro model systems. The cell lines included PLC/PRF/5 (Alexander cell line), Hep3B. HepG2, TONG PHC, HA22T/VGH, HA59T/VGH and Mahlavu, The cell lines K562 and Raji were used as negative and positive controls, respectively. K562, a B tymphoid-derived cell line, was shown to express negligible amounts of human leucocyte anligens, while Raji, an erythromyeloid-derived cell line, expressed both class I and class II human leucocyte anligens as well as their respective invariant chains, ^2-niicroglobulin and Ii. Using an ELISA, experiments performed on these cell lines confirmed the natural expression of class I and class II antigens by the HA22T/VGH and HA59T/VGH cell lines, whereas PLC/PRF/5 displayed class II surface antigens only. The effects of modulating agents such as interferon-gamma sodium bulyrate and clofazimine on human leucocyte antigen expression were investigated using the HA22T/VGH, HA59T/VGH and TONG PHC cell lines. These agents increased class 1 and class II human leucocyte antigen expression on HA22T/VGH and TONG PHC cells, but had no effect on the HA59T/VGH cell line. The results suggest a potential use for these agents as modulators of human leucocyte antigen expression by human heptocellular cell lines.

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“…Clofazimine, however, has been reported to inhibit leukocyte migration and mitogen-induced proliferation (8,18) and has been reported to be useful, in high dosage, in controlling both ENL (10,20) and reversal immunity reactions (13,17) inhibitory effects of the drug on PMNL migration (8,18). In borderline cases with residual specific cell-mediated immunity and reversal immunity reactions, the beneficial immunosuppressive effects of clofazimine are probably attributable to inhibition of leukocyte migration and proliferation (8,18). In this study, the effects of clofazimine, dapsone, and rifampin on PG E2 synthesis by human PMNL in vitro were investigated.…”

Section: Effectsmentioning

confidence: 99%

“…Direct and indirect enhancement of cell-mediated immunity by dapsone may lead to the development of reversal immunity reactions (2). Clofazimine inhibits lymphocyte proliferation (8,18) and may be useful in controlling reversal immunity reactions (13,17). We have suggested previously that the anti-inflammatory, immunosuppressive properties of clofazimine and the nonspecific immunostimulatory effects of dapsone are related to the respective proand anti-oxidant activities of these agents (2,18).…”

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Enhancement by clofazimine and inhibition by dapsone of production of prostaglandin E2 by human polymorphonuclear leukocytes in vitro

Anderson

1985

Antimicrob Agents Chemother

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The effects of the antileprosy agents clofazimine and dapsone (1 to 10 ,ig/mi) on the spontaneous and stimulated release of prostaglandin E2 (PG E2) by human polymorphonuclear leukocytes (PMNL) in vitro have been investigated. PMNL were obtained from normal adult volunteers and three patients with leprosy (two borderline lepromatous and one subpolar lepromatous leprosy). The synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) at a concentration of 10-7 M was used as the stimulant of PG E2 synthesis. None of the test agents at the concentrations used inhibited the binding of radiolabeled FMLP to PMNL. However, dapsone at 5 and 10 ,ug/ml inhibited the spontaneous and FMLP-induced release of PG E2 by PMNL. Clofazimine, on the other hand, significantly Increased both the spontaneous and the FMLP-induced synthesis of PG E2 by PMNL. The enhancing effects of clofazimine on FMLP-mediated synthesis of PG E2 were particularly striking and were observed at concentrations of 1 to 10 jig of the drug per ml. Measurements of PMNL spontaneous and FMLP-induced synthesis of PG E2 in the presence of both clofazimine and dapsone (5 ,ug/ml) indicated that the two drugs are mutually antagonistic. PMNL from both normal control subjects and patients with leprosy were equally sensitive to these effects of clofazimine and dapsone. The immunostimulatory and immunosuppressive properties of dapsone and clofazimine, respectively, may be related to the opposite effects of these agents on PG E2 synthesis in human leukocytes.

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Thein vitroandin vivoeffects of clofazimine on the motility of neutrophils and transformation of lymphocytes from normal individuals

Cited by 8 publications

References 0 publications

Multitarget Approaches against Multiresistant Superbugs

Multitarget Approaches against Multiresistant Superbugs

HLA expression in hepatocellular carcinoma cell lines

Enhancement by clofazimine and inhibition by dapsone of production of prostaglandin E2 by human polymorphonuclear leukocytes in vitro

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