Related Experiment Videos
Immunomodulation of pneumococcal pulmonary infection with N(G)-monomethyl-L-arginine
Y Bergeron1, N Ouellet, M Simard
1Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Département de Microbiologie, Faculté de Médecine, Université Laval, Sainte-Foy, Québec, Canada G1V 4G2.
Abstract:
It has recently become apparent that inflammatory reactions including nitric oxide (NO) release contribute to the outcome of pulmonary infections. To investigate the effect of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, on the pathogenesis of pneumococcal pneumonia, we inoculated CD(1) Swiss mice with 10(7) CFU of Streptococcus pneumoniae. Treatment with two daily subcutaneous injections of 3 mg of L-NMMA per kg of body weight (over a 5-day period) reproducibly delayed mortality, as the number of surviving mice 72, 84, and 96 h after infection was increased by 16.8% (P < 0.05), 25.0% (P < 0.005), and 11.5% (P < 0. 05), respectively. In fact, the following chronology of events was noted in L-NMMA-treated infected animals, compared to the untreated infected controls. (i) At 12 to 24 h after infection, larger amounts of leukotriene B(4) in bronchoalveolar lavage (BAL) fluid associated with greater neutrophilia in lung tissue and alveolar spaces and more persistent release of tumor necrosis factor alpha, interleukin-1 alpha (IL-1alpha), and IL-6 were observed. (ii) At 24 to 72 h, there was better preservation of lung ultrastructure, including reduction of edema in the interstitium and protection of alveolar spaces, despite identical bacterial growth in lungs, in L-NMMA-treated infected animals than in untreated animals. (iii) At 72 to 96 h, the death rate was delayed, despite the absence of antibiotic therapy. In our experiment, partial blockade of NO release was achieved. These data indicate that NO plays an important role in the induction of tissue injury and death during pneumococcal pneumonia and that L-NMMA is helpful for host protection.
Insights
Nitric oxide (NO) inhibition with L-NMMA delayed mortality in pneumococcal pneumonia by reducing inflammation and tissue damage. This study highlights NO
Area of Science:
- Pulmonary Medicine
- Immunology
- Microbiology
Background:
- Inflammatory responses, including nitric oxide (NO) release, impact pulmonary infection outcomes.
- Pneumococcal pneumonia is a significant respiratory infection with potential for severe outcomes.
Purpose of the Study:
- To investigate the effect of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, on the pathogenesis of pneumococcal pneumonia.
- To determine if inhibiting NO production can mitigate disease severity and improve host survival.
Main Methods:
- CD(1) Swiss mice were inoculated with Streptococcus pneumoniae.
- Mice received daily subcutaneous injections of L-NMMA (3 mg/kg) for 5 days.
- Outcomes including survival rates, inflammatory markers, and lung tissue integrity were assessed.
Main Results:
- L-NMMA treatment significantly delayed mortality in infected mice.
- Inhibition of NO led to reduced leukotriene B(4) and neutrophilia early in infection.
- L-NMMA treatment preserved lung ultrastructure and reduced edema, despite similar bacterial loads.
Conclusions:
- Nitric oxide plays a critical role in inducing tissue injury and mortality during pneumococcal pneumonia.
- Partial blockade of NO release using L-NMMA demonstrates a protective effect on the host.
- Targeting NO pathways may represent a therapeutic strategy for pneumococcal pneumonia.