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
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.