IHC revealed the presence of an inflammatory infiltrate consistin

IHC revealed the presence of an inflammatory infiltrate consisting predominantly of neutrophils, which presented a heterogeneous pattern of distribution. A difference in cell morphology was also observed: in sections with fewer neutrophils these cells were well

compacted, whereas in sections presenting larger numbers this cell type was characterized by a larger size and cytoplasmic content (Fig. 5a). IL-8 was strongly expressed (Fig. 5c) and iNOS was moderately expressed (Fig. 5e) in all the lesions examined. Infiltrate neutrophils, IL-8 and iNOS were not detected in controls (Fig. 5b,d,f ). The outcome of Leishmania infection is determined by the delicate balance that exists among a large array of cytokines expressed by the cellular infiltrate at the site of infection. In this study, we observed concomitant expression of both macrophage-activating and de-activating cytokines within Everolimus order cutaneous lesions caused by L. tropica GPCR Compound Library supplier infection. Analysis of cytokine gene expression in the CL lesions revealed elevated levels of IFN-γ, IL-10, TNF-α, IL-1β, IL-8, IL-4, MCP-1 and iNOS, suggesting that CL results from an exacerbated and improperly modulated Th1 immune response. Although IFN-γ, TNF-α and NO are products that are necessary to kill Leishmania,19 they

are also implicated in the inflammation leading to tissue damage in other infections.20,21 IFN-γ and TNF-α are important in defence mechanisms against parasites; however, overproduction of these cytokines does not necessarily lead to parasite clearance and may even be harmful to the host. IFN-γ and IL-10 mRNAs were co-expressed in 100% of the lesions, click here and a significant correlation (0·84) was observed; this extends previous observations of concomitant expression of these cytokines in patients with CL22 and in VL.18 These two cross-regulatory cytokines have contrasting effects on the host response against intracellular pathogens.23 IL-10 expression has previously been described to be significantly higher

in the more slowly healing lesions in patients with CL caused by L. major22 and is a promoter of persistent disease in patients infected with L. mexicana.8 In our study, IL-10 expression correlated strongly with both TNF-α and IL-8 (0·95), while the expression of TNF-α and IL-8 also correlated (0·89). IL-8, also known as monocyte-derived neutrophil chemotactic factor, is a strong neutrophil chemotactic and activating cytokine.24 The potential importance of IL-8 in the pathogenesis of inflammatory diseases has been suggested by findings of increased synthesis in adult respiratory distress syndrome, rheumatoid arthritis, idiopathic pulmonary fibrosis and central nervous diseases.24–26 A positive correlation of TNF-α and IFN-γ with IL-8 indicated that both may synergistically induce IL-8 production, as reported in earlier studies.

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