Post-exposure protection with rNAPc2 against Ebola virus in primates provides a new foundation for therapeutic regimens that target the disease process rather than viral replication.
Here we describe a lethal mouse model infected with dengue virus type 2 with several similarities to human DEN-2 infection. Clinically animals demonstrated anemia, thrombocytopenia, pre-terminal paralysis and shock. The most impressive changes were seen with tumor necrosis factor (TNF)-alpha, which abruptly and steeply increased 24 h before the exitus (mean at day 6). Serum levels of IL-1beta, IL-6, IL-10, IL-1 receptor antagonist and soluble TNF receptor I continuously increased during the time of infection. A 100% mortality rate was noted in that group of animals. Treating animals with anti-TNF-alpha serum reduced mortality rate down to 40% (P<0.05). Our model supports the view that activation of innate immune response is at least partially responsible for mortality in DEN-2 infection, and in line with this concept, anti-TNF treatment significantly reduces mortality rates.
SUMMARY Tick-Borne Encephalitis virus (TBEV) causes dangerous central nervous system diseases in humans.General infection leads to the development of meningitis or encephalitis, which is characterized by swelling of the brain due to inflammation. Tetracyclines may act locally to moderate inflammation in the CNS. In this study, we investigated the potential clinical benefits of administering tetracycline hydrochloride to patients hospitalized due to suspected TBEV infection presenting with fever and evidence of a recent tick bite. We also characterized an acute immune response to TBEV by profiling certain cytokines and soluble receptors in Tetracycline-treated and untreated patients. Increased serum levels of TNF-a , IL-1 a and IL-6 were found in all patients at admission.Soluble receptors presented in the serum of patients in a magnitude higher levels than the corresponding cytokines and were increasing during first weak of hospitalization. Levels of IL-10 were also rising during that period. In our study tetracycline hydrochloride acted as an immunomodulator, which was able to reduce manifestations of inflammation response during TBE course; this action led to quicker improvement of symptoms and, consequently, to a faster clinical recovery. The positive result of tetracycline hydrochloride treatment was accompanied by certain particularities in the dynamics of studyied cytokines and receptors: the concentrations of IL-6, IL-1 b , TNF-a dropped quicker and reached lower levels, and the concentrations of sIL-6R, IL-1RA, sTNFR1 increased faster and reached higher maximum levels in the tetracycline-treated groups. Children had the highest levels of IL-6, which were not neurotoxic.
During the months of November 1996, August 1997, and March 1998, saliva and plasma samples were collected for isolation of aerobic bacteria from 26 wild and 13 captive Komodo dragons (Varanus komodoensis). Twenty-eight Gram-negative and 29 Gram-positive species of bacteria were isolated from the saliva of the 39 Komodo dragons. A greater number of wild than captive dragons were positive for both Gram-negative and Gram-positive bacteria. The average number of bacterial species within the saliva of wild dragons was 46% greater than for captive dragons. While Escherichia coli was the most common bacterium isolated from the saliva of wild dragons, this species was not present in captive dragons. The most common bacteria isolated from the saliva of captive dragons were Staphylococcus capitis and Staphylococcus capitis and Staphylococcus caseolyticus, neither of which were found in wild dragons. High mortality was seen among mice injected with saliva from wild dragons and the only bacterium isolated from the blood of dying mice was Pasteurella multocida. A competitive inhibition enzyme-linked immunosorbent assay revealed the presence of anti-Pasteurella antibody in the plasma of Komodo dragons. Four species of bacteria isolated from dragon saliva showed resistance to one or more of 16 antimicrobics tested. The wide variety of bacteria demonstrated in the saliva of the Komodo dragon in this study, at least one species of which was highly lethal in mice and 54 species of which are known pathogens, support the observation that wounds inflicted by this animal are often associated with sepsis and subsequent bacteremia in prey animals.
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