Lesion size correlates with Leishmania antigen-stimulated TNF-levels in human cutaneous leishmaniasis

Abstract

Cutaneous leishmaniasis (CL) is a worldwide disease endemic in several regions of the globe. The hallmark of CL is skin ulcers likely driven by efforts of the immune system to control Leishmania growth. Cytokines, such as tumor necrosis factor (TNF) and interferon-gamma can control disease progression in animal models. Nevertheless, the impact of these cytokines in CL ulcer outcome is not well established in humans. In this study, 96 CL patients from an endemic area of Leishmania braziliensis were enrolled for a follow-up study that consisted of clinical and immunological evaluations in a 2-year period. Statistical analysis revealed that healing time (P = 0.029), age (P = 0.002), and TNF levels (P = 0.0002) positively correlate with ulcer size at the time of the first clinical evaluation. Our findings suggest that ulcer size correlates with healing time and TNF levels support the use of TNF inhibitors combined with standard therapy to improve healing in CL patients with severe lesions.

Figure 1.

Positive correlation between lesion size and healing time, age, or tumor necrosis factor (TNF) levels on cutaneous leishmaniasis (CL) patients. (A) Correlation between healing time (days) and lesion size (cm) (N = 70). (B) Correlation between patient age (years) and lesion size (cm) (N = 70). (C) Correlation between TNF levels in the supernatant measured by enzyme-linked immunosorbent assay (ELISA) (pg/mL) and lesion size (cm) (N = 52). The solid line represents the linear regression and the dotted line the 95% predicted coefficient interval. The Spearman correlation coefficient is designated in each figure by “r_s.”

Figure 2.

Positive correlation between cytokine levels on cutaneous leishmaniasis (CL) patients. (A) Correlation between tumor necrosis factor (TNF) and interferon-gamma (IFN- γ) levels (pg/mL) (N = 52). (B) Correlation between TNF and interleukin-10 (IL-10) levels (pg/mL) (N = 52). (C) Correlation between IFN- γ and IL-10 levels (pg/mL) (N = 52). The solid line represents the linear regression and the dotted line the 95% predicted coefficient interval. The Spearman correlation coefficient is designated in each figure by “r_s.”

Figure 3.

Comparison between lesion size and number of courses of Sb^V on cutaneous leishmaniasis patients. Data represent mean ± standard deviation of the measurements of lesion size in the group of patients that received either a single or several (two or three) courses of Sb^V during the study. The Mann-Whitney test was performed. (*) denotes statistical significance with P < 0.05.