Related Experiment Video
Updated: Aug 26, 2026
Advanced Imaging of Lung Homing Human Lymphocytes in an Experimental In Vivo Model of Allergic Inflammation Based on Light-sheet Microscopy
Published on: April 16, 2019
Blockade of endogenous leukotrienes exacerbates pulmonary histoplasmosis
Alexandra I Medeiros1, Anderson Sá-Nunes, Edson G Soares
1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil.
Abstract:
Leukotrienes are classical mediators of inflammatory response. New aspects of leukotriene function have recently been described. We examine here the previously unreported role that leukotrienes play in the regulation of cytokines in a murine model of histoplasmosis. We demonstrate that administration of MK 886, a leukotriene synthesis inhibitor, caused Histoplasma capsulatum-infected mice to die by the day 15 of infection, whereas the correlating death rate in untreated infected mice was 0%. Treating infected animals with MK 886 inhibited leukotriene synthesis but increased leukocyte recruitment to the lungs. Subsequent to this phenomenon, levels of tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and KC chemoattractant cytokines and fungi in the lung parenchyma increased, as did inflammatory response. In contrast, IL-2, IL-5, IL-12, and gamma interferon cytokine levels actually decreased. Thus, murine response to pulmonary histoplasmosis may be leukotriene modulated. This finding may enable us to alter the course of the immune response and inflammation caused by histoplasmosis. The data from the present study suggest an important new strategy for immunologic or drug intervention in human patients.
Insights
Leukotriene inhibition worsened histoplasmosis in mice, increasing fungal load and inflammatory cytokines. This suggests leukotrienes are crucial for controlling this fungal infection and may offer new therapeutic targets.
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- Leukotrienes are key mediators in inflammatory responses.
- Emerging research reveals novel functions of leukotrienes.
- Their role in fungal infections like histoplasmosis remains largely unexplored.
Purpose of the Study:
- To investigate the role of leukotrienes in regulating cytokines during murine histoplasmosis.
- To determine the impact of inhibiting leukotriene synthesis on the host immune response to Histoplasma capsulatum.
Main Methods:
- Utilized a murine model of pulmonary histoplasmosis.
- Administered MK 886, a leukotriene synthesis inhibitor.
- Assessed survival rates, leukocyte recruitment, cytokine levels (TNF-α, IL-1, IL-6, KC, IL-2, IL-5, IL-12, IFN-γ), and fungal burden in the lungs.
Main Results:
- MK 886 treatment led to 100% mortality in infected mice by day 15, compared to 0% in controls.
- Inhibition of leukotriene synthesis increased leukocyte infiltration into the lungs.
- Elevated levels of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, KC) and fungal burden were observed.
- Decreased levels of anti-inflammatory/regulatory cytokines (IL-2, IL-5, IL-12, IFN-γ) were noted.
Conclusions:
- Murine pulmonary histoplasmosis is significantly modulated by leukotrienes.
- Leukotriene synthesis inhibition exacerbates the disease, suggesting a protective role for leukotrienes.
- These findings present a potential new strategy for immunologic or drug-based interventions in human histoplasmosis.
Related Concept Videos
01:23Chronic Obstructive Pulmonary Disease II: Emphysema
01:21Antiprotozoal Agents
01:28Pulmonary Tuberculosis II
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
01:24Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features