[A study of possibility to predict the sensitivity of different respiratory tract divisions to influenza].

To predict a potential value of a viral ID50 for a macro-organism of interest (e.g. humans), it is necessary to determine in vitro two parameters of the interaction of the virus with susceptible cells of the host, i.e. the probability of the virus' productive absorption on a susceptible cell and the average virus yield per cell. A different macroorganism (a model animal) and primary cells obtained from it can be used to determine the value of a scale factor, which accounts for the difference between the values of the probability of the virus' absorption measured in vivo and in vitro. An original mathematical model is used to convert the above-mentioned data to ID50 for the macroorganism of interest. It was shown that the method of cultivating influenza virus (A/ Aichi/2/68) in primary suspension culture of respiratory tract cells of rats and two breeds of mice may be used to estimate potential human susceptibility to novel influenza viruses. This work was sponsored by DAPRA, USA, and performed under the contract 450p to the International Science and Technology Center, Moscow.

[Target-cell susceptibility and lung phagocyte activity in mice with influenza virus resistance lowered by glucocorticoidal immunosuppression].

The results of the study showed that subcutaneous kenalog (Kn) lowered the resistance of mice to influenza virus (InV), as was seen by a decrease in 50% lethal dose and an increase in the degree of pulmonary tissue lesion, and the susceptibility of the lungs to InV, seen by the fact that 50% aerogenic infective dose (AID50) was significantly higher in the main group (Kn+InV) than in controls, which received Hanks solution subcutaneously (HS+InV). In vitro, 50% infective doses of InV for suspension of pulmonary and tracheal cells, characterizing their susceptibility to InV, were similar in Kn mice and controls. At the same time, lower resistance and higher degree of pulmonary inflammation noted in Kn mice after receiving a dose of InV that was much higher than an infecting one, was accompanied by the prevalence in the number as well as phagocyte and superoxide-producing activity of neutrophiles (Nph) over the same parameters for alveolar macrophages (AMph) as early as two days after receiving InV dose, vs. InV-infected controls. Evidently, one of the reasons for lower resistance to InV after Kn administration is significant disbalance between the functional activity of AMph and Nph populations. Ineffective AMph clearance of the lungs from InV and excessive number of recruited Nph and products of tissue disintegration may favor the development of respiratory failure and infectious-toxic shock, which leads to lower resistance in animals which receive Kn before InV infection.

[The influence of glucocorticoid immunosuppression on the course of experimental influenza pneumonia].

The study demonstrates the effects of kenalog (Kn), a synthetic glucocorticoid hormone, on the course of virus A/Aichi/2/68 influenza in white mice. In doses of 5 and 10 mg/kg, Kn reduced the weight of the adrenal glands, thymus and spleen, which was accompanied by decrease of the resistance to the mentioned virus, judging by LD50 decrease vs. this index in the control infected group. Besides, four days after infecting with 5 LD50 of influenza virus (IV), lung virus and interferon titers were significantly lower in mice pretreated with Kn vs. mice treated with placebo. Lung cell susceptibility to IV in vitro was identical in mice treated with Kn or placebo. In ultrathin lung sections of IV-infected mice, both experimental and control ones, there was virus budding in bronchial epithelium cells and type I and II alveolocytes. Analysis of inflammatory effusion compound in semithin lung sections 6 days after IV infection, found a substantially smaller number of mature alveolar macrophages (AM) and a bigger number of neutrophiles vs. infected controls. The authors reckon that higher mortality of mice pretreated with Kn before infecting, is caused not by enhancement of IV reproduction in target lung cells during influenza development, but by the contribution of other pathogenic factors. One of those may be increase of neutrophilic migration into the lungs; neutrophiles are more able to realize their significant destructive potential under the condition of reduction in the clearing function of AM and IV infection.

[Pulmonary cell susceptibility in mice and rats to influenza virus when infected in vivo and in vitro]. / Vospriimchivost' kletok legkikh u myshei i krys k virusu grippa pri infitsirovanii in vivo i in vitro.

The purpose of the case study was to evaluate comparatively the relative contribution of cell susceptibility and the inhibiting effect of factors of pulmonary epithelial lining in mice and rats to influenza virus A/Aichi/2/68 (H3N2) adapted to mice as related with the development of infection process in the lungs of experimental animals when infected in vivo and in vitro. Mice and rats were infected aerogenically with different doses of influenza virus. The primary cell-culture suspensions sampled from the lungs of mice and rats were used to study the adsorption and dynamics of influenza virus production in infection by different dose of influenza virus in vitro. The cell suspensions were shown to be able to produce the influenza virus for as long as 48 hours after infection. It was for the first time that the results denoted the identical susceptibility of primary pulmonary cells in mice and rats to influenza virus. A lower pulmonary susceptibility to influenza virus in rats versus mice could be indicative of that the surface factors of epithelial lining contribute essentially to shaping the pulmonary susceptibility to influenza virus since there is no difference of the susceptibility of pulmonary cells to influenza virus between the two above animals' species.