Dear Editor,

We read with great interest the contribution by Handler1 about how high doses of hydralazine can induce the development of lupus. However, he did not explain the association between hydralazine use and occurrence of lupus. We would like to comment on a possible mechanism concerning the development of lupus by using hydralazine.

Xu and colleagues2 reported that there were decreases in the production of interleukin (IL) 10 at higher concentrations of hydralazine. IL-10 has been known as a pleiotropic cytokine that possesses immunosuppression properties.3 Ling and colleagues reported that IL-10 prevented induction of lupus-like renal end-organ damage by down-regulating pathogenic Th1 responses.4 Blenman and colleagues showed that continuous overexpression of IL-10 delayed antinuclear autoantibody products and decreased clinical nephritis.5

Yin and colleagues demonstrated MRL-Fas(lpr) IL-10(−/−) mice developed severe lupus, and higher mortality than IL-10-intact controls.6 In this study, increasing severity of lupus in IL-10(−/−) mice was associated with increased interferon-γ production by both CD4(+) and CD8(+) cells and serum concentration of IgG2a anti–ds-DNA autoantibodies.

Therefore, there is a possibility that high doses of hydralazine may decrease IL-10 and promote the development of lupus. However, further studies are necessary to examine the dose of hydralazine that may induce lupus and to elucidate the pathways of IL-10 in the condition.


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  2. References
  • 1
    Handler J. Hydralazine-induced lupus erythematosis. Clin Exp Pharmacol Physiol. 2009;36:1839842.
  • 2
    Xu B, Thornton C, Tooher J, et al. Effects of anti-hypertensive drugs on production of soluble fms-like tyrosine kinase 1 and soluble endoglin from human normal and pre-eclamptic placentas in vitro. Crit Care Med. 2009;36:839842.
  • 3
    Oberholzer A, Oberholzer C, Moldawer LL. Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med. 2002;30:S58S63.
  • 4
    Ling GS, Cook HT, Botto M, et al. An essential pretective tole of IL-10 in the immunological mechanism underlying resistance vs. susceptibility to lupus induction by dendritic cells and dying cells. Rheumatology (Oxford). 2011;50:17731784.
  • 5
    Blenman KR, Duan B, Xu Z, et al. IL-10 regulation of lupus in the NZM2410 murine model. Lab Invest. 2006;86:11361148.
  • 6
    Yin Z, Bahtiyar G, Zhang N, et al. IL-10 regulates murine lupus. J Immunol. 2002;169:21482155.