IL6−174 G/C Promoter Polymorphism Influences Susceptibility to Mucosal but Not Localized Cutaneous Leishmaniasis in Brazil

Léa Castellucci, Eliane Menezes, Joyce Oliveira, Andrea Magalhães, Luiz Henrique Guimarães, Marcus Lessa, Silvana Ribeiro, Jeancarlo Reale, Elza Ferreira Noronha, Mary E. Wilson, Priya Duggal, Terri H. Beaty (+6 others)
2006 Journal of Infectious Diseases  
Background. Mucosal leishmaniasis (ML) is associated with exaggerated tumor necrosis factor-a and interferon-g responses and tissue destruction. ML follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis infection. Interleukin (IL)-6 down-regulates T helper (Th) cell type 1 differentiation and drives Th2 cell differentiation. The IL6 Ϫ174 G/C polymorphism is associated with proinflammatory diseases and IL-6 regulation. Methods. The Ϫ174 G/C polymorphism was genotyped in
more » ... population samples and families with CL and ML from Brazil. Genotype frequencies were compared among patients with ML, patients with CL, and 2 control groups by logistic regression and family-based association test (FBAT) analysis. IL-6 levels were measured in macrophages. Results. The C allele was more common in patients with ML than in patients with CL ( odds ratio [OR], 2.55 [95% confidence interval {CI}, 1.32-4.91]; ), than in patients who were leishmanin skin-test positive (OR, P p .005 2.23 [95% CI, 1.23-4.05]; ), and than in neighborhood control subjects (OR, 2.47 [95% CI, 1.24-4.90]; P p .009 ). FBAT analysis confirmed an association between allele C and ML under both additive ( ; P p .01 z p 4.295 ) and dominant ( ; ) models. Significantly lower levels of IL-6 were measured in P p .000017 z p 4.325 P p .000015 unstimulated macrophages from CC individuals than from GG individuals ( ) as well as after stimulation P p .003 with soluble leishmania antigen ( ). P p .009 Conclusions. IL-6 may regulate type 1 proinflammatory responses, putting individuals with low macrophage IL-6 levels at increased risk for ML. Leishmaniasis is a protozoan parasitic infection transmitted by sand flies. Different species of Leishmania are
doi:10.1086/505504 pmid:16845637 fatcat:dtk7hyz4hbcg5n4u5znb7biblq