Suppression of macrophage activation with CNI-1493 increases survival in infant rats with systemic Haemophilus influenzae infection

Citation
C. Granert et al., Suppression of macrophage activation with CNI-1493 increases survival in infant rats with systemic Haemophilus influenzae infection, INFEC IMMUN, 68(9), 2000, pp. 5329-5334
Citations number
31
Categorie Soggetti
Immunology
Journal title
INFECTION AND IMMUNITY
ISSN journal
00199567 → ACNP
Volume
68
Issue
9
Year of publication
2000
Pages
5329 - 5334
Database
ISI
SICI code
0019-9567(200009)68:9<5329:SOMAWC>2.0.ZU;2-8
Abstract
CNI-1493, a potent macrophage deactivator, was used to treat infant rats sy stemically infected with Haemophilus influenzae type b (Hib). CNI-1493 was injected 1 h prior to bacterial inoculation and 24 h later and resulted in a 75 percent increased rate of survival compared to that for untreated cont rols. The effect of CNI-1493 on the inflammatory response was studied by im munohistochemical detection of individual tumor necrosis factor alpha (TNF- alpha)-, interleukin 1 beta (IL-1 beta)-, and gamma interferon (IFN-gamma)- producing cells in the spleen. A significant reduction of the incidence of TNF-alpha- and IL-1 beta-expressing cells was found for CNI-1493-treated an imals. IFN-gamma expression was not suppressed by CNI-1493, indicating that cytokine inhibition was specific in macrophages. CNI-1493 significantly re duced the number of infiltrating granulocytes in the brain from that for co ntrols. This study provides evidence that CNI-1493 protects against lethal Hib infection by deactivating the inflammatory cascade in infant rats.