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It is revealed that Roncoleukin (12.5 mg/kg, intraperitoneally, 5 injections a day), Betaleukin (0.1 mg/kg, intraperitoneally, 1 time in 3 days (5 weeks)), Bestim (0.1 mg/kg, intraperitoneally, 10 injections), cycloferon (3.6 mg/kg, intraperitoneally, 3 times a week for 6 weeks), Glutoxim (40 mg/kg subcutaneously (4 weeks)and the preparation of succinic acid remaxol (at a dose of 25 mg/kg intraperitoneally, daily 14 introduction), when you enter them in a comprehensive drug therapy pilot MDR tuberculosis in mice produce a positive effect on the regression of inflammation in the lung tissue, stimulate local immunity of the lungs, activate and digestive absorption capacity of peritoneal macrophages an average of 1.4 and 1.9, p0.05, inhibited the tuberculosis infection and chemotherapy.

The results of pre-clinical research of cycloferon, remaxol and runihol on the model of experimental generalized tuberculosis, caused by the MBT with a different spectrum of drug sensitivity are presented. A considerable increase of the curative effect of the therapy with the used of cycloferon and remaxol. There was manifested the strengthening of lung clearance from the office, reducing the prevalence of specific inflammation in the lungs of the index of lung damage, stimulation of sorption and destructive ability of peritoneal macrophages, inhibited in the course of development of experimental tuberculosis infection. Runihol has no impact on the effectiveness of chemotherapy in the absence of a stimulating influence on the phagocytic function of the peritoneal macrophages.

Experiments on 160 male albino outbred rats investigated the hepatoprotective activity of S-adenosyl-L-methionine (SAM) and runihol in liver damage caused by subtoxic doses of reserve-series antituberculous drugs (ATD) (PASA, cycloserine, prothionamide) and their combination. It was established that a combination of ATDs had the maximum hepatotoxic activity, cycloserine had the least. There was evidence that SAM versus runihol had a more pronounced ability to correct ATD-induced evolving cytolysis syndrome. Histological study indicated that SAM and runihol also showed a marked hepatoprotective effect. When added to PASA, prothionamide, or a combination of ATDs, both drugs promoted recovery of the hepatic architectonics and a reduction in the prevalence of albuminous dystrophy. The use of SAM additionally led to activation of alterative processes in the hepatic parenchyma.

The results of an experimental study of the efficiency of cycloferon included in a complex chemotherapy of generalized drug-resistant mycobacterium tuberculosis (MBT) are presented. It is established that cycloferon (3.6 mg/kg) produces a significant therapeutic effect, which is manifested by an increase in the lung clearance from MBT, a decrease in the spread of specific inflammation in the lungs, and the disappearance of MBT-induced alterations. In addition, activation of the signs of tension in the local immunity of lung tissues is observed as manifested by changes in the cellular composition of granulomas and more frequent detection of large lymphocytic and macrophage infiltration. The administration of cycloferon significantly increases the absorptive and digestive activity of phagocytosis by peritoneal macrophages, which has been inhibited during the development of experimental MBT infection.

Efficacy of remaxol in complex chemotherapy of generalized drug resistant tuberculosis was studied on mice. Mycobacterium tuberculosis 5419 SPBNIIF isolated from a patient with freshey diagnosticated pulmonary tuberculosis resistant to isoniazid (10 mcg/ml), rifampicin (40 mcg/ml), streptomycin (10 mcg/ml) and ethionamide (30 mcg/ml) was used in the experiments. The main polychemotherapy included 4 antituberculosis drugs in the highest therapeutic doses: isoniazid, amikacin, ethambutol and tavanic, the treatment course was 8 weeks. Remaxol was administered in a dose of 25 ml/kg intraperitoneally 5 times a week (14 injections). Significant activating effect of remaxol on the tension of the lung tissue local immunity was revealed by changes in the granuloma cell composition (from mainly epitheliod to mainly lymphoid) and by more frequent large lymphohistiocytic infiltrates. The use of remaxol also greatly increased the absorptive and digestive activity of the peritoneal macrophages phagocytosis, inhibited in the process of the experimental tuberculosis development.

The use of Flu/ESAT-6 in chemotherapy for experimental tuberculosis has been found to cause a significant improvement of its results, which appears as the higher clearance of lung tissue from mycobacteria, the reduced extent of specific inflammation foci, and the altered cell composition of granulomas with mainly epithelioid to mainly lymphoid one. Flu/ESAT-6 of Tx-1 immunity (spontaneous and phytohemagglutinin-induced proliferation of splenocytes, spontaneous production of gamma-IFN) and ESAT-6-specific stimulation of a cell immune response (the proliferative activity of splenic lymphocytes and the production of IL-2 in response to recESAT-6) is shown to activate. The influenza vector A/PR8/NS1-125 that contains no ESAT-6 insert shows immunoadjuvant properties, which is likely to cause some reduction in the severity of tuberculosis in the control group of the vaccine.

In vitro experiments showed that islacet produced an inhibitory effect on the growth of laboratory drug-sensitive Mycobacterium strains when used at a concentration of 25 microg/ml. A considerable reduction in death rates and a significant decrease in the mass index and in the indices of pulmonary lesion and bacterial isolation from splenic homogenates were observed on the model of generalized tuberculosis in mice and rabbits given islacet. In parallel with the higher efficiency of therapy using islacet, there was ConA- and PPD- stimulated proliferation of splenocytes and their production of interleukin-2 drastically inhibited in mice that had long received multidrug therapy (HRZ and HRE). Islacet was found to enhance the functional activity of phagocytes and that inhibited during the development of infection and under the influence of long-term (more than 1 month) etiotropic therapy: the generation of superoxide by murine peritoneal macrophages and rabbit neutrophils, as well as by the absorptive and digestive function of peritoneal macrophages.

The synthetic dipeptide bestim was tested for effects on the functional activity of peritoneal macrophages on 400 non-inbred albino mice while simulating generalized tuberculosis of varying severity (classical, acutely progressive, and slowly progressive). Bestim was shown to have a stimulating effect on the activity of macrophageal phagocytosis of yeast cell suspension. The agent was also found to exert a restorative effect on the absorptive and digestive functions of macrophages during their inhibition during infection and under the influence of long-term (more than a month) etiotropic therapy. Bestim showed an activating effect on the content of extracellular 5-nucleotidase during the classical and acutely progressive course of infection. It was shown to have a modulating effect on the macrophageal generation of superoxide radicals, by enhancing the inhibited HCT activity in acutely progressive infection and by reducing the elevated level of superoxide production in slowly progressive tuberculosis. In slowly progressive tuberculosis, the drug produced a stimulating effect on the adhesive activity of macrophages.

Studies dealing with the design of new antituberculous agents based on goal-oriented synthesis have provided the agent Perchlosone which is similar to isoniazid and rifampicin, produces in tuberculostatic activity against sensitive laboratory cultured mycobacteria, produces an inhibitory action on polyresistant clinical strains. Experiments on animals (mice, rabbits) with experimental tuberculosis have established that Perchlosone and isoniazid have equal therapeutical properties, and the former shows a synergist interaction with rifampicin, has neither mutagenic activity nor negative effects on immunity and the surfactant system of the lung.

Mice with experimental tuberculosis were given isoniazid, rifampicin, erythromycin, cefotaxime, ofloxacin. Erythromycin, cefotaxime and ofloxacin enhanced macrophage activity if their course did not exceed 2-4 weeks. Isoniazid and rifampicin for a short time inhibited macrophage activity then stimulated it. These findings led the authors to the conclusion that erythromycin, cefotaxime and ofloxacin must be used only in short courses.

The experimental studies have provided strong evidence that the efficacy of etiotropic therapy for tuberculosis can be enhanced by applying a number of antimicrobial agents having different mechanism of action, which belong to cephalosporins, macrolides, aminoglycosides, fluoroquinolones. The basis of the mechanism responsible for potentiation of activity of essential tuberculostatic drugs for potentiation of activity of essential tuberculostatic drugs is enhanced inhibition of the viability of a microbacterial population, prevented development of drug resistance in tuberculosis mycobacteria, and increased function of macrophages.

Cephalosporin antibiotics cefamezin (I generation drug sensitive to beta-lactamase) and cefotaxime (III generation drug resistant to beta-lactamase) have been tested for antituberculous activity. The latter was found dependent on resistance to mycobacterial beta-lactamase. A minimal inhibiting concentration of cefotaxime was similar to that of etambutol and tisamid. Cefotaxime also enhanced tuberculostatic and bactericidal effect of isoniazid and rifampicin. Combination cefotaxime+isoniazid+rifampicin proved more effective than cefotaxime+etambutol+tisamid. The effectiveness against tuberculosis of the beta-lactamase resistant cephalosporin points to the validity of further research for active phthisiatric drugs among III generation cephalosporins.