A obesidade e o tecido adiposo na patogênese e gravidade da Leishmaniose cutânea

Abstract

Obesity is associated with worse clinical outcomes in cutaneous leishmaniasis (CL). Here, we evaluated the influence of obesity on the systemic, dermal, and adipose tissue immune responses in CL. A total of 39 obese and 43 individuals with normal BMI with ulcerated CL caused by Leishmania braziliensis confirmed by PCR were enrolled, along with 8 healthy subjects (HS), 4 with normal BMI and 4 obese. Peripheral blood mononuclear cells (PBMC) were cultured for 72 hours in the presence or absence of soluble Leishmania antigen (SLA, 5 μg/mL). Skin and adipose tissue biopsies were analyzed histologically, and cytokines and adipokines were quantified after 72-hour incubation. All patients were treated with meglumine antimoniate. The cure rate was lower in obese patients (41%) compared to those with normal BMI (70.4%) (p < 0.05). No significant differences in proinflammatory cytokine production were observed in PBMC supernatants. However, cytokines (IL-1β, IL-17, Granzyme B) and leptin were significantly higher in skin biopsies of obese compared to normal BMI CL patients (p < 0.05), and leptin levels correlated directly with these cytokines in both groups. Adipose tissue was infiltrated by inflammatory cells, with larger inflammatory areas in obese CL patients (p < 0.05). Cytokines were largely undetectable in adipose tissue, except for elevated CCL2. Notably, leptin and adiponectin levels were markedly increased in CL patients compared to HS, suggesting infection-driven modulation of adipocyte function. These findings demonstrate that CL enhances adipokine production and that obesity amplifies local inflammatory responses, contributing to greater disease severity and therapeutic failure in obese individuals.