Reactive nitrogen intermediate production and tolerance variability in different mouse strains after in vivo treatment with lipopolysaccharide from Salmonella abortus equi

Hossein Nahrevanian¹, Jafar Gholizadeh Salmasi², Mahin Farahmand¹, Zohreh Aghighi¹, Mehdi Assmar¹, Mohsen Abolhassani³
Departments of ¹Parasitology, ²Education and ³Immunology, Pasteur Institute of Iran, Tehran, Iran

Received: February 1, 2005 Revised: March 20, 2005 Accepted: March 28, 2005

Corresponding author: Dr. Hossein Nahrevanian, Department of Parasitology, Pasteur Institute of Iran, Pasteur Avenue, Tehran 13164, Iran. E-mail:

Lipopolysaccharide (LPS) stimulation in animal models generates a large number of immune factors including cytokines and mediators. It also acts as a potent inducer of macrophage reactive oxygen intermediates and reactive nitrogen intermediates (RNI). RNI as stable metabolites of nitric oxide (NO) are produced by cells stimulated with LPS and cytokines. In this study, LPS from Salmonella abortus equi was investigated as an inducer of RNI in untreated controls and test groups of white Naval Medical Research Institute (NMRI) mice. Animals were humanely killed at 30, 60, 120 and 180 min after LPS injection, and plasma RNI was measured by Griess microassay. In a further experiment, host tolerance against bacterial LPS was evaluated by sequential intravenous injection of LPS concentrations of 4, 1 and 0.5 mg/kg at 24 h intervals in NMRI and with the same schedule but via subcutaneous injection in Balb/c mice. Statistical analysis of RNI values using analysis of variance test indicated that in vivo LPS stimulation induced high levels of NO in murine hosts (p<0.001). Comparison of RNI levels at different times after administration revealed the largest amount of RNI at 180 min after inoculation. Analysis of the time course until maximum RNI induction indicated that NMRI mice had the longest delay, suggesting a difference in tolerance of NMRI and Balb/c mice to LPS stimulation dependent on LPS concentration, dose, and route of inoculation.

Key words: Inbred BALB C mice, lipopolysaccharides, nitric oxide, reactive nitrogen species

J Microbiol Immunol Infect2005;38:164-168.