Anti-inflammatory actions of dapsone and its related biochemistry

Williams, Katrina; Capstick, R B; Lewis, David; Best, R.

doi:10.1111/j.2042-7158.1976.tb02794.x

Cited by 34 publications

(11 citation statements)

References 12 publications

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“…In vitro experiments with other bacteria have shown that the chemotherapeutic agent has sulfonamide-like antimicrobial properties and causes inhibition of the enzyme dihydropteroic acid synthetase (13). However, it seems unlikely that this is the only mechanism (if it is indeed a true in vivo mechanism) since dapsone has been reported to have beneficial effects in non-mycobacterial diseases such as dermatitis herpetiformis (9), generalized pustular psoriasis (19), and leukocytoclastic vasculitis (27) and in some cases of rheumatoid arthritis (26) and Crohn's disease (23). The effects of dapsone therapy observed in these conditions may relate to the anti-inflammatory activity of the drug (22).…”

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confidence: 99%

In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy

Gatner¹,

Rensburg²,

Grabow³

et al. 1981

Antimicrob Agents Chemother

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The effects of dapsone on polymorphonuclear leukocyte functions and lymphocyte mitogen-induced transformation were assessed in vitro and in vivo in normal individuals and in newly diagnosed untreated patients with lepromatous leprosy. The effects of dapsone on the cell-free generation of superoxide by the xanthine:xanthine oxidase system and iodination of bovine serum albumin by horseradish peroxidase were also investigated. In normal individuals dapsone mediated stimulation of polymorphonuclear leukocyte migration in vitro and in vivo. Dapsone had no effects on postphagocytic hexose monophosphate shunt activity or superoxide generation in vitro, but caused slight inhibition of peroxidase-mediated protein iodination in vitro and in vivo and hexose monophosphate shunt activity in vivo. Sirnilar effects were found in patients with lepromatous leprosy. Dapsone also decreased the inhibitory activity of serum from patients with lepromatous leprosy on normal polymorphonuclear leukocyte migration in vitro. Progressive loss of serum-mediated inhibition of migration was observed after ingestion of dapsone by the patients. Further experiments showed that stimulation of polymorphonuclear leukocyte motility was related to inhibition of the peroxidase-H202-halide system in vitro. The drug caused inhibition of lymphocyte transformation at high concentrations in vitro, but had slight stimulatory activity on phytohemagglutinin-induced transformation in controls and patients in vivo.

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confidence: 99%

In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy

Gatner¹,

Rensburg²,

Grabow³

et al. 1981

Antimicrob Agents Chemother

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“…In high doses over a prolonged period of time, dapsone appears to suppress the Arthus reaction in guinea pigs (11). Dapsone also shows anti-inflammatory activity comparable with established nonsteroidal anti-inflammatory drugs such as indomethacin (9). Furthermore, an inhibition of lysosomal enzyme release comparable with that of corticosteroids has been shown (12).…”

Section: Introductionmentioning

confidence: 86%

“…It is well known that dapsone (4,4'-diaminodiphenyl sulfone) has a dramatically beneficial effect on DH (3 subcorneal pustular dermatosis (6), generalized pustular psoriasis (7), leukocytoclastic vasculitis (8), and recently, in some cases of rheumatoid arthritis (9) and Crohn's disease (10). Immune complexes have been implicated in the pathogenesis of most of the disorders mentioned.…”

Section: Introductionmentioning

confidence: 99%

The Inhibition of Polymorphonuclear Leukocyte Cytotoxicity by Dapsone

Stendahl¹,

Molin²,

Dahlgren³

1978

J. Clin. Invest.

178

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A B S T R A C T The effect of the sulfone compound 4,4'-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 ,ug/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H202-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaL. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the 51Cr release from virus-induced lymphoma cells. Because the MPO-H202-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system.

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“…Ultra violetinduced erythema in the guinea pig is an exception although its relevance has never been fully understood. Dapsone, an anti-leprotic agent that possesses antiinflammatory activity (Williams, Capstick, Lewis & Best, 1976;Lewis, Gemmell & Stimson, 1978) inhibited both the early phase (0-1.5 h) and late phase (1.5-4 h) of the response. However, dapsone was more effective at 1.5 h (oral ED50 34 mg/kg) than at 3 h (oral ED50 60 mg/kg).…”

Section: Poster Communicationsmentioning

confidence: 99%