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

CNI-1493, a potent macrophage deactivator, was used to treat infant rats systemically 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 controls. The effect of CNI-1493 on the inflammatory response was studied by immunohistochemical detection of individual tumor necrosis factor alpha (TNF-alpha)-, interleukin 1 beta (IL-1beta)-, and gamma interferon (IFN-gamma)-producing cells in the spleen. A significant reduction of the incidence of TNF-alpha- and IL-1beta-expressing cells was found for CNI-1493-treated animals. IFN-gamma expression was not suppressed by CNI-1493, indicating that cytokine inhibition was specific in macrophages. CNI-1493 significantly reduced the number of infiltrating granulocytes in the brain from that for controls. This study provides evidence that CNI-1493 protects against lethal Hib infection by deactivating the inflammatory cascade in infant rats.