A novel mechanism of action of the

A novel mechanism of action of the antimalarials
has recently been elucidated with respect to its inhibition
of toll-like receptor (TLR) 9 family receptors.1
TLRs are intracytoplasmic receptors whose activation
of the innate immune system in response to microbial
peptides induces a significant inflammatory response.
Additionally, further research has highlighted the
importance of the innate immune response underlying
the pathogenesis of systemic lupus erythematosus
(SLE).23 Consequently, these TLRs who, as a class,
are known as “pattern recognition receptors” (PRRs),
have become a subject of intense investigation underlying
the pathogenesis of SLE. It has recently been
shown that host immune complexes containing DNA
or RNA play an important role in activating endogenous
TLRs (especially TLR-9 and TLR-7), thus leading
to the eventual activation of the innate immune system,
of which interferon alpha plays a crucial role.24,25
Additionally, TLR-9 expression is strongly associated
with SLE activity.25 These specific nucleic acid binding
TLRs bind their ligands in the lysosome, where
an acidic environment promotes this binding.26 As the
antimalarial agents specifically target microsomes by
disrupting endosomal maturation and changing the
pH, they block the TLR interaction (TLR-3, -7, and -9)
with nucleic acid ligands.27 In vitro studies have identified
that nanomolar
concentrations of chloroquine specifically
were potent inhibitors of IL-6 production by
monocytes, an effect now known to be directly mediated
by the inhibition of TLR-9.1 Antigen presenting
cells are the primary targets of these interactions, thus
accounting for a clinically slower response, as they
initiate and prime the subsequent immune reactions.1
The 4-aminoquinolines have an affinity for melanin
pigment. In the epidermis (as well as retina), they bind
in high concentrations. In the skin, CQ absorbs ultraviolet
(UV) light in a concentration-dependent manner.28
There is an increase in minimal erythema doses (MEDs)
to UVB in lupus patients after taking oral chloroquine
for 3 months, theoretically resulting from the antiinflammatory
and/or photoprotective mechanisms of
the drugs.1,29 Topical CQ applied before UV irradiation
protects against UVB- and UVA-induced erythema.30
QE has also been shown to inhibit photodynamic
actions.31 It has been proposed that the beneficial effect
of the HCQ and CQ in various photodermatoses may
result from the ability of these drugs to enhance the
protective early limb of the UV response.32

Hasil (Bahasa Indonesia) 1:

Novel mekanisme kerja dari antimalarialsBaru-baru ini terungkap terkait dengan penghambatan nyatol-seperti reseptor (TLR) 9 receptors.1 KeluargaTLRs adalah reseptor intracytoplasmic aktivasi yangsistem kekebalan tubuh bawaan dalam menanggapi mikrobapeptida menginduksi respon inflamasi yang signifikan.Selain itu, lebih lanjut penelitian telah menyorotipentingnya respon imun bawaan yang mendasaripatogenesis lupus eritematosus sistemik(SLE).23 Akibatnya, ini TLRs yang, sebagai kelas,dikenal sebagai "pola pengakuan reseptor" (PRRs),telah menjadi subyek intens penyelidikan yang mendasaripatogenesis SLE. Baru-baru ini telahditunjukkan host kompleks imun yang mengandung DNAatau RNA memainkan peran penting dalam mengaktifkan endogenTLRs (terutama TLR-9 dan TLR-7), sehingga mengarahakhirnya aktivasi sistem kekebalan tubuh bawaan,mana interferon Alfa memainkan role.24,25 pentingSelain itu, ekspresi TLR-9 sangat terkaitdengan SLE activity.25 ini mengikat asam nukleat yang spesifikTLRs mengikat ligan mereka di Lisosom, manamempromosikan lingkungan asam binding.26 ini sebagaiAgen obat secara khusus menargetkan microsomes olehmengganggu endosomal pematangan dan mengubahpH, mereka blok interaksi TLR (TLR-3, -7, dan -9)dengan asam nukleat ligands.27 penelitian secara In vitro telah mengidentifikasinanomolar itukonsentrasi klorokuin khususadalah inhibitor poten produksi IL-6monosit, efek sekarang dikenal untuk langsung ditengahioleh penghambatan menyajikan Antigen TLR-9.1sel-sel adalah target utama interaksi, sehinggaakuntansi untuk respon klinis lebih lambat, karena merekamemulai dan Prima reactions.1 kebal berikutnya4-aminoquinolines memiliki afinitas untuk melaninpigmen. Epidermis (serta retina), mereka mengikatdalam konsentrasi tinggi. Dalam kulit, CQ menyerap ultraungu(UV) lampu di manner.28 tergantung pada konsentrasiAda peningkatan dalam dosis minimal eritema (obat-obatan)untuk UVB penderita lupus setelah mengambil klorokuin lisanselama 3 bulan, secara teoritis dihasilkan dari antiinflamasidan/atau mekanisme photoprotectivedrugs.1,29 CQ topikal diterapkan sebelum iradiasi UVmelindungi terhadap UVB dan UVA-diinduksi erythema.30QE juga telah ditunjukkan untuk menghambat photodynamicActions.31 itu telah diusulkan bahwa efek menguntungkanHCQ dan CQ dalam berbagai photodermatoses dapathasil dari kemampuan obat ini untuk meningkatkanpelindung dahan awal UV response.32