1. ¹Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil
2. ²Seção de Enteroparasitoses, Instituto Adolfo Lutz, São Paulo, Brazil
3. ³Biochemistry Department, Trinity College, Dublin, Ireland

Correspondence: Dr M De Franco, Laboratório de Imunogenética, Instituto Butantan, Av. Vital Brazil 1500, São Paulo, SP 05503900, Brazil. E-mail: mdfranco@butantan.gov.br

Received 17 August 2006; Revised 12 October 2006; Accepted 16 October 2006; Published online 23 November 2006.

Abstract

Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax^RR, AIRmax^SS, AIRmin^RR and AIRmin^SS lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax^RR mice reached 29%, whereas PIA incidence in AIRmax^SS mice was 70% by day 180. AIRmin^RR mice were resistant, whereas 13.3% of AIRmin^SS mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1^SS mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.