SLE: Study defines positive responders to antimalarials

New findings indicate that antimalarial agents effectively reduce TNF-alpha levels in patients with systemic lupus erythematosus (SLE). The authors also identify that responses were greatest in those with high levels of TNF-alpha and low levels of interleukin (IL)-10.The researchers, led by Dr Ana Suarez (University of Oviedo, Spain), evaluated cytokine levels in 171 SLE patients and 215 healthy controls. The group also genotyped polymorphisms at promoter regions of the two cytokines in 192 SLE patients and 343 controls, to explore genetic predictors for a response to antimalarial therapy.Suarez's group report that TNF-alpha levels were similar in controls (19.66 pg/mL) and SLE subjects (n=39) treated with antimalarials alone for at least three months (16.64 pg/mL). However, TNF-alpha levels were higher for those who were untreated or were receiving treatment with NSAIDs, corticosteroids, or immunosuppressive drugs (60.01-105.34 pg/mL).The authors suggest that their finding indicates that antimalarial-mediated inhibition of TNF-alpha is only significant in patients who were genetically high TNF-alpha or low IL-10 producers. Additionally, evaluation of SLE patients administered antimalarial drugs for three or more years, who did not require any other specific SLE treatment, "indicates that patients with the combined genotype low IL-10/high TNFa are the best responders to antimalarial therapy." They also suggest that there is a regulatory feedback mechanism that leads to decreases in TNF-alpha transcription in patients producing elevated amounts of IL-10. "Thus," they say, "our results suggest that antimalarial agents require a high rate of TNF-alpha transcription to achieve the maximal inhibitory effect."In concluding, Suarez's group comment, "antimalarial-mediated downregulation of TNFa levels in SLE patients is influenced by polymorphisms at IL-10 and TNFa promoters... Taken in conjunction, these results thus indicate that determination of TNF-alpha and IL-10 alleles at the onset of the disease may help identify more suitable candidates for antimalarial treatment and could be used as a genetic predictor of clinical outcome."Reference...