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Objective: This study was designed to evaluate therapeutic effects of bindarit, an indazolic derivative able to inhibit monocyte chemoattractant protein-1 (MCP-1) production, in adjuvant induced arthritis in rats.¶ Materials and methods: Arthritis was induced by Freund's complete adjuvant injection. Bindarit was given as a 0.5% medicated diet starting on day 11 after adjuvant injection. The course of arthritis was monitored by sequential paw volume measurement and by radiologic and histologic evaluations. Human osteoblast cell line Saos-2 stimulated with Interleukin-1 (IL-1) was used to assess in vitro bindarit effect on MCP-1 release. In addition, in vivo effects of bindarit on cytokine production were studied in mice injected with lipopolysaccharide (LPS). Immune function studies were performed in mice by evaluating ex vivo antibody response to ovalbumin and splenocytes proliferation to Concanavalin A (Con A).¶ Results: In adjuvant-induced arthritis in rats, bindarit possessed therapeutic activity resulting in a significant inhibition of paw inflammation. Evidence for a disease-modifying activity was also indicated by amelioration of radiologic alterations and by histological evaluation of joints. Additional evidence for beneficial effects in osseous inflammation was provided by an in vitro assay in which bindarit inhibited the release of MCP-1 from IL-1 stimulated osteoblast cells. Moreover, in a murine model of LPS-induced cytokine production bindarit reduced MCP-1 and tumor necrosis factor (TNF)-α increase without affecting IL-1 and IL-6 levels. Finally, the drug, given as a 0.5% medicated diet for 14 days, did not affect either anti-ovalbumin serum antibody production or splenocytes proliferative response in mice.¶ Conclusions: Results obtained indicate that bindarit beneficial effects in experimental arthritis are correlated to MCP-1 and TNF-α inhibition and suggest that the control of cytokines and chemokines production can have considerable relevance as regards strategies for the treatment of chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Benzydamine is a non-steroidal antiinflammatory drug, devoid of activity on arachidonic acid metabolism, which is extensively used as a topical drug in inflammatory conditions, particularly for the treatment of bacterial vaginosis and Candida albicans-sustained vaginitis. In the present study the effects of benzydamine on the production of several inflammatory cytokines were examined in cultures of Candida albicans-stimulated human mononuclear cells. Benzydamine (6.25-50 ΜM) inhibited Candida-induced tumor necrosis factor-α and, to a lesser extent, interleukin-1 Β production, whereas it did not affect interleukin-6 release. Benzydamine also blocked monocyte chemotactic protein-1 secretion, but it did not affect interleukin-8 production. Unlike benzydamine, ibuprofen and naproxen, two non-steroidal antiinflammatory drugs also used topically, were unable to suppress inflammatory lymphokine production from Candida-activated mononuclear cells. These data suggesrthat benzydamine may be effective in local Candida infections at least in part by suppressing inflammatory cytokine and monokine production in the vaginal mucosa and consequently decreasing their levels in vaginal secretions. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have shown that benzydamine (40 mg/kg s.c.) is able to inhibit tumor necrosis factor (TNF) production and to reduce mouse lethality when administered before or concomitantly with LPS. The present study was designed to further investigate benzydamine activity against LPS-induced toxicity in terms of potency and therapeutic effects.¶ Methods: Female Balb/c mice were used. A dose-response curve of animal lethality versus endotoxin dose was performed (LD50 = 45 μg/mouse). Therapeutic effects were studied selecting the dose of LPS to achieve an LD100 (160 μg/mouse). Mortality was assessed daily and mice were followed for 8 days. The potential mode of action of therapeutically administered benzydamine was also investigated. TNFα and IL-1β levels were measured, at 5 h after LPS injection, both in sera and in lungs. Moreover, the drug was assayed in a TNF-dependent cytoxicity test.¶ Results: Benzydamine, administered at 20 mg/kg s.c. simultaneously with the endotoxin, significantly increased LPS LD50 up to 230 μg/mouse (p < 0.05). Moreover, the drug significantly protected mice against LPS-induced lethality when administered either 30 min or 4 h after endotoxin injection (p < 0.001). Benzydamine, therapeutically administered at 20 mg/kg s.c., significantly reduced TNFα and IL-1β production induced by LPS both in serum and lungs and it was shown to inhibit TNF-dependent cytoxicity on L929 cells.¶ Conclusions: These results clearly demonstrate the therapeutic activity of benzydamine in a simple model of endotoxic shock. Available data confirm the potential role of benzydamine as an anti-cytokine agent and provide suggestions for novel therapeutic applications of this anti-inflammatory drug. [ABSTRACT FROM AUTHOR]

The production and action of primary proinflammatory cytokines are strictly controlled by a series of circuits to avoid damage that they can cause if produced in excess. Interleukin-10 and interleukin-1 receptor antagonist contribute to the control of the magnitude of the inflammatory responses in vivo. Benzydamine, a non-steroidal anti-inflammatory drug that has been shown to have suppressive activity for the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β, was investigated for its effects on interleukin-10 and interleukin-1ra production. The drug did not modify the production of interleukin-10 and interleukin-1ra by peripheral blood mononuclear cells stimulated with lipopolysaccharide, under conditions where tumor necrosis factor-α and interleukin-1β were decreased. The antiinflammatory capacity of benzydamine might thus result from its ability to reduce the production of proinflammatory cytokines, without affecting antiinflammatory factors. [ABSTRACT FROM AUTHOR]