The Expression of Inflammatory Mediators and its Association with the Susceptibility to Mucosal Leishmaniasis in Peru

Abstract Leishmania braziliensis can cause cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) in humans, and the latter is characterized by excessive T- and B-cell responses. We hypothesized that conversion from CL to ML is partially due to an imbalanced production of proinflammatory and regulatory cytokines, leading to uncontrolled host responses to the parasites. To test this hypothesis, we first examined the -2518 SNP of the MCP-1 promoter because its G/G genotype is associated with autoimmune disorders and infectious diseases. We genotyped 142 Peruvian subjects (18 controls, 65 CL and 59 ML patients) using PCR-RFLP on genomic DNA. Our pilot studies suggested that ML patients showed a relatively frequency for the MCP-1 G/G genotype (28/62, 45%) than the A/A (9/22, 41%) or A/G genotypes (2/58, 38%), respectively. Using dot blot analysis, we detected higher levels of MCP-1, IFN-γ, IL-8, IP10, MIP-1β, -1d, and soluble TNF receptors in the sera of CL and ML patients as compared with the healthy controls. Additional quantitative studies confirmed that sera of ML patients contained significantly higher levels of IP-10, MIP-1β and sTNFRII when compared to CL and healthy controls. This study suggests that the over-production of inflammatory cytokines is a contributing factor to the pathogenesis of mucosal lesions. Studies are ongoing to define the sources of these inflammatory mediators.