Pathogenesis of Leishmania donovani induced cutaneous leishmaniasis: role of Tumor Necrosis Factor α

Abstract

BACKGROUND: Cutaneous leishmaniasis (CL) in Sri Lanka is caused by the usually visceralizing Leishmania donovani. Host immune response plays a key role in the clinical presentation of leishmaniasis. Role of cytokines in pathogenesis of local lesions has not been studied. OBJECTIVE: To describe tissue cytokine expression with lesion progression with time in CL due to Leishmania donovani. METHODS: Skin biopsies from fifty eight patients with parasitologically or histopathologically confirmed CL and 30 healthy controls were analyzed for local tissue expression of Interleukin (IL)-12A, IL-4, IL-10, Interferon-gamma (IFNg) and Tumor Necrosis Factor-alpha (TNF-α). Cytokine mRNA was quantified by real-time RT- PCR using SYBR green. Relative copy numbers were calculated for each gene by 2-ΔΔCt method using β-actin as the reference gene and healthy controls as the calibrator. Spearman correlation was used to determine the correlation between cytokines and duration of active skin lesions. RESULTS: The study group consisted of 37 males (63.8%) and 21 females (36.2%) with a mean age of 35 (SD=12.05) years which ranged between 18-66 years. Mean duration of lesions was 6.8 (SD=9.10) months with a range of 1-48 months. The Spearman correlation coefficient for relative copy numbers and lesion duration was 0.220, 0.077, 0.073, 0.235 and 0.295 for IL-12A, IL-4, IL-10, IFNg and TNF-α respectively. There was a significant positive correlation between expression of TNF-α and lesion duration (p= 0.024). CONCLUSIONS: Localized expression of TNF-α increases with time in CL due to L. donovani in Sri Lanka, which indicates development of a pro-inflammatory immune response at the site of infection as the disease progresses.