Pneumonia remains one of the major medical problems, gaining more and more economic and social significance, despite rich studies on the processes of lung disease [1,2]. There is no doubt that rational antibiotic therapy by itself is not capable of solving the outcome of the disease: much depends on the macroorganism, its individual immunoreactivity and resistance [5].

The immune system is one of the most sensitive in the body, reacting quickly to contact with damaging agents. Activated cells of the immune system secrete cytokines, the study of which is important in terms of interpreting disorders in the functional vitality of the body’s immune system, assessing the severity, monitoring the effectiveness of an ongoing therapy, predicting the course and outcome of pneumonia.Cytokines are involved in the inflammatory process that develops in the lungs, provoking effects that are expressed in changes in hemodynamics, impaired microcirculation, the formation of alveolar and interstitial edema, the development of hypoxia as well as metabolic pulmonary malfunction. The balance of pro-inflammatory and anti-inflammatory cytokines in inflammation largely determines the direction, severity and outcome of pneumonia [3,4,6].

Objective of the study. To study local IFNγ and IL-10 production in the dynamics of pneumonia development depending on its etiology.

Materials and methods. The research has been conducted on non-inbred white mice weighing 18-25 g obtained from the nursery of laboratory animals of the Research Institute of Experimental Medicine, NR Russian Academy of Medical Sciences, Vladivostok. A model of experimental pneumonia has been obtained by intranasal infection of mice with bacterial strains isolated from BALJ of patients with defined diagnosis of pneumonia, in a dose corresponding to LD50. A series of experiments has been performed with different strains of microorganisms: Pseudomonas aeruginosa (experiment 1), Enterobacter species (experiment 2), Escherichia coli (experiment 3), Staphylococcus aureus (experiment 4). The material for the study was collected on the 1st and 3rd days of the experiment by decapitation of laboratory animals under ether anesthesia. Cytokine production was assessed by their levels in the supernatant of lung tissue homogenized by enzyme linked immunosorbent assay (ELISA) using reagents from R&D system Inc. (murine IFNy, murine IL-10). The results were processed using Wilcoxon W-test and Mann-Whitney U-test modules of SPSS v16.0 statistical package. Normality of the distribution was checked by the Kolmogorov-Smirnov method. The critical value of the W-criterion significance level was assumed to be 0.062, U-criterion-0.032 at the confidence level of 0.05 for the number of groups n1=5 and n2=5.

Results and discussion. The early cytokine response in mice infected with NP pathogens was characterized by a predominance of IL-10 production both on the 1st and the 3rd day after infection. The maximum mean concentrations of oppositional cytokines were recorded in relation to cytokine indices in mice infected with Enterobacter spp. There was found a significant difference in IFN content on the 1st day after infection between experimental pneumonia, caused by Enterobacter spp. and pneumonia, caused by E. coli (131.92±23.48 pg/ml versus 65.93±9.78 pg/ml, pU=0.032). At infection of experimental animals with P. aeruginosa the most expressed decrease of IFN content in a supernatant of a pulmonary tissue (40.45±5.85 pg/ml, pU=0.008) was observed. The IFN level in staphylococcal experimental pneumonia on the 1st day after infection was practically unchanged in comparison with IFN values in intact animals (77.77±5.55 pg/ml and 74.33±6.79 pg/ml respectively). On the 3rd day from the moment of infection, local IFN production in Pseudomonas influenzae mice was decreased (32.26±4.07 pg/ml, pW=0.080), while in other variants of experimental pneumonia, on the contrary, IFNγ concentration was increased. The significant difference between indices was fixed at E. coli induced pneumonia (91.35±7.57 pg/ml, pW=0.043). IFN level was also significantly increased in pneumonia caused by S. aureus (119.34±4.14 pg/ml, pW=0.043).

Increase of anti-inflammatory cytokine IL-10 concentration after 1 day occurred in all variants of experimental pneumonia in comparison with local IL-10 level in intact mice (85.03±5.08 pg/ml). The maximal concentration of IL-10 was registered in the study in enterobacterial pneumonia (375.18±68.86 pg/ml), the least altered IL-10 level — in E. coli-induced pneumonia (103.64±8.13 pg/ml). On the 3rd day after infection, IL-10 level continued to increase in experimental pneumonia caused by P. aeruginosa (165.95±16.87 pg/ml, pU=0.225) and in pneumonia caused by S. aureus (226.28±16.99 pg/ml, pU=0.225). At E. coli induced pneumonia, insignificant decrease of IL-10 level up to 90.88±5.89 pg/ml (pU=0.080), more expressed decrease of IL-10 was registered on the 3rd day at experimental pneumonia, caused by Enterobacter spp. (261.77±26.93 pg/ml, pU=0.225). IL-10 level in this pneumonia on the 3rd day after infection was significantly higher than that in pseudomonas caused by E. coli (pU=0.032) and in pneumonia caused by E. coli (pU=0.008).

Conclusions. Type of a causative agent influences local cytokine response at pneumonia: P. aeruginosa causes pronounced suppression of proinflammatory cytokine IFNγ production; at infection of mice with Enterobacter spp. there is increase of IFNγ. In all variants of experimental pneumonias there is an early activation of anti-inflammatory cytokine IL-10, which is not a good prognostic sign, as early and excessive production of anti-inflammatory cytokines changes the sequence of anti-infective defense mechanisms and aggravates the course of the inflammatory process. The type of pathogen affects the local cytokine response in pneumonia: P. aeruginosa causes a pronounced inhibition of pro-inflammatory cytokine IFN production; when mice are infected with Enterobacter spp. In all variants of experimental pneumonia there is an early activation of anti-inflammatory cytokine IL-10, which is not a good prognostic sign, since early and excessive production of anti-inflammatory cytokines changes the sequence of anti-infective defense mechanisms and aggravates the course of inflammation.