Session Type: Abstract Submissions (ACR)
Toll-like receptor 9 (TLR-9) plays an important role in initiating innate immunity. The recognition of self DNA fragments by TLR-9 may results in the production of interferon-α, a central cytokine in the pathogenesis of Systemic lupus erythematosus (SLE). Anti-malarial drugs such as hydroxychloroquine (HCQ) and quinacrine (Qn) are commonly used in the treatment of SLE. Some studies imply that anti-malarial drugs may influence TLR pathway, though detail mechanisms are still under study. In this study, we want to evaluate the influence of anti-malarial drugs (HCQ and Qn) on the initiation of IFN-α production through TLR-9 pathway, combinded with or without glucocorticoid.
Freshly isolated PBMCs of healthy donors were stimulated with the TLR-9 agonist CpG oligodeoxynucleotides (CpG-A ODN)-2216, then incubated with different kinds of anti-malarial drugs ( HCQ and Qn or both) and / or different doses of glucocorticoid (hydrocortisone: 10-6M (low dose), 10-5M (median dose), 10-4M (high dose), 10-3M (pulse dose)). The changes in the expression of IFN-α were detected by real time PCR.
(1). Hydroxychloroquine or quinacrine alone or combined together significantly inhibited the production of IFN-α initiated by ODN 2216 (Qn (p=0.047), HCQ (p=0.047), Qn and HCQ (p=0.046)). (2). When combined with low (10-6M), median (10-5M), or high (10-4M) dose of hydrocortisone, HCQ or Qn or both significantly revised the elevation of IFN-α caused by ODN 2216 ((low dose: Qn (p=0.017), HCQ (p=0.017), Qn & HCQ (p=0.017), median dose: Qn (p=0.034), HCQ (p=0.032), Qn & HCQ (p=0.036), high dose: Qn (p=0.028), HCQ (p=0.024), Qn & HCQ (p=0.028)), which cannot be decreased by glucocorticoid (each p>0.05). (3). When combined with pulse dose (10-3M) hydrocortisone which could promote the expression of IFN-α to some extent, anti-malarial drugs (HCQ, Qn alone or both) could not significantly down-regulate the expression of IFN-α stimulated by ODN 2216.
(1). Anti-malarial drugs hamper the production of IFN-α by TLR-9 recognition of nucleotides (ODN 2216), which is the critical cytokine in the pathogenesis of lupus. (2). The combination with anti-malarial drugs (HCQ, Qn alone or both) seem to be a good choice to help low, median, high dose glucocorticoid to achieve a better disease control by inhibiting IFN-α, which cannot be decreased by glucocorticoid. (3). When combined with pulse dose glucocorticoid, anti-malarial drugs (HCQ, Qn alone or both) could not down-regulate the expression of IFN-α stimulated by TLR-9 agonist.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-malarial-drugs-hydroxychloroquine-and-quinacrine-decrease-the-production-of-interferon-alfa-initiated-by-tlr-9-agonist/