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.

Age Modifies the Immunologic Response and Clinical Presentation of American Tegumentary Leishmaniasis

“…8,[23][24][25] During the early stages of the infection, before the appearance of an ulcer, there is a down modulation of IFNγ mediated by IL-10. 26 There is also evidence that IL-10 plays a major role in the pathogenesis of the disease.…”

“…Another prospective study showed a positive correlation between CL ulcer size and age in patients with CL caused by L. braziliensis infection. 8 Moreover, age has been an important factor regarding side effects caused by antimony therapy. 9,10 Epidemiologic studies have pointed out that ATL occur predominantly in young subjects, a population that is more exposed to sand fly bites.…”

Leishmaniasis in rheumatology, haematology and oncology: epidemiological, immunological and clinical aspects and caveats

“…There is strong evidence from mouse experiments with various Leishmania species62 and from clinical observations (see below) that TNF is indispensable for the control of the parasites (figure 1). On the other hand, TNF and other factors that exert cytotoxic activities (eg, Fas ligand, TNF-related apoptosis-inducing ligand) are implicated in the formation of skin ulcers in CL 64 65…”

Chronic infection by Leishmania amazonensis mediated through MAPK ERK mechanisms

“…The main sand-fly vector of L. amazonensis is Lutzomyia flaviscutellata [4]. There are hundreds of sand-fly species, but only 30 of them are documented to transmit Leishmania spp.…”

“…There are hundreds of sand-fly species, but only 30 of them are documented to transmit Leishmania spp. CL ulcers tend to become necrotic in the center and are elevated at the sides [4]. Lymphadenopathy, or enlarged lymph nodes, has been reported to precede ulcer formation [5].…”