New concepts in antimalarial use and mode of action in dermatology

Kalia, Sunil; Dutz, Jan P.

doi:10.1111/j.1529-8019.2007.00131.x

Cited by 237 publications

(219 citation statements)

References 153 publications

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“…There is now sufficient validation around certain TLRs to justify them as therapeutical targets (6,7). Curiously, antimalarial drugs were widely used for the treatment of IMIDs long before their inhibitory effect on intracellular TLRs was recognized (8).…”

mentioning

confidence: 99%

Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria

Franklin

Ishizaka

Lamphier

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

106

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Excessive release of proinflammatory cytokines by innate immune cells is an important component of the pathogenic basis of malaria. Proinflammatory cytokines are a direct output of Toll-like receptor (TLR) activation during microbial infection. Thus, interference with TLR function is likely to render a better clinical outcome by preventing their aberrant activation and the excessive release of inflammatory mediators. Herein, we describe the protective effect and mechanism of action of E6446, a synthetic antagonist of nucleic acid-sensing TLRs, on experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA. We show that in vitro, low doses of E6446 specifically inhibited the activation of human and mouse TLR9. Tenfold higher concentrations of this compound also inhibited the human TLR8 response to single-stranded RNA. In vivo, therapy with E6446 diminished the activation of TLR9 and prevented the exacerbated cytokine response observed during acute Plasmodium infection. Furthermore, severe signs of ECM, such as limb paralysis, brain vascular leak, and death, were all prevented by oral treatment with E6446. Hence, we provide evidence that supports the involvement of nucleic acid-sensing TLRs in malaria pathogenesis and that interference with the activation of these receptors is a promising strategy to prevent deleterious inflammatory responses that mediate pathogenesis and severity of malaria.immunotherapy | innate immunity | nucleic acid recognition | inflammation

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mentioning

confidence: 99%

Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria

Franklin

Ishizaka

Lamphier

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

106

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“…Mais recentemente foi proposto novo mecanismo de ação por meio da inibição de receptor toll-like. Baixas concentrações de cloroquina mostraram prevenir de maneira acentuada a produção de interleucina-6 induzida por bactérias em células mononucleares humanas do sangue periférico, efeito resultante da inibição de receptor toll-like-9 (TLR-9) (11) .…”

Section: Resultsunclassified

Avaliação do uso da hidroxicloroquina no tratamento da osteoartrite sintomática de joelhos

Bonfante¹,

Machado²,

Andrade³

et al. 2008

Rev. Bras. Reumatol.

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“…These drugs have been prescribed for rheumatic diseases, several inflammatory conditions and immune related skin disorders (9) . Most recently these drugs have been used in conjunction with anti-neoplastic chemo-or radiotherapies, where induction of autophagy has been shown to function as an escape mechanism for neoplastic cells to evade death.…”

Section: Hydroxychloroquine: a New Spin On An Old Conceptmentioning

confidence: 99%