CCL2, CCL18 and sIL-4R in renal, meningeal and pulmonary TB; a 2 year study of patients and contacts.

The role of Th2 cytokines and Th2-associated chemokines in tuberculosis (TB) remains controversial, though in Mexico a polymorphism causing increased production of CCL2 is a risk factor. We studied levels of the Th2-associated chemokines CCL2 and CCL18, circulating soluble IL-4 receptors (sIL-4R), IL-4 and the inhibitory splice variant of IL-4 (IL-4δ2) in a cohort of patients with pulmonary TB and their healthy contacts. These were followed for 2 years during which time 10 contacts developed pulmonary TB. Results were compared with measurements made in renal and meningeal TB, and in disease controls with bacterial pneumonias or Dengue fever that have large Th2 components. In these disease controls both chemokines were significantly raised. They were also very significantly raised in all forms of TB, irrespective of age or disease site. Levels of CCL18 were raised least in meningeal TB, and most in pulmonary patients with long histories, when levels were similar to those in disease controls. Levels of CCL2, although also raised in all three forms of TB, were negatively correlated with CCL18. We found that levels of sIL-4R were strikingly reduced in all forms of TB, particularly meningeal. Contacts who progressed could not be distinguished from contacts who remained healthy at 2 years in terms of IL-4, sIL-4R, CCL2 or CCL18. However contacts had raised expression of IL-4δ2 as previously found. These results indicate vigorous and previously unrecorded activity within the Th2 axis, and further investigation is warranted.

[SPECIFIC IMMUNE RESPONSE AND PROTECTIVE FACTORS OF NEUTROPHIL GRANULOCYTES IN PULMONARY AND EXTRAPULMONARY TUBERCULOSIS].

An immune response and protective factors of neutrophil granulocytes were comparatively studied in 61 patients with pulmonary tuberculosis, 70 with nephrotuberculosis, and 45 with tuberculous spondylitis. It was shown that there were elevated serum levels of neutrophil cationic proteins in both pulmonary and extrapulmonary tuberculosis. Lower content of intracellular cationic proteins along with suppressed cellular immunity was observed in pulmonary tuberculosis patients with disseminated actively progressive changes. This combination may be regarded as a poor predictor. Higher values of a specific cellular immune response and elevated levels of intracellular cationic proteins of neutrophils were found in extrapulmonary tuberculosis. This was also seen in patients with severe clinical manifestations of the disease. Thus, there is reason to believe that there is a regulatory association of the protective factors of neutrophil granulocytes with cellular immunity in tuberculosis.

[Expression of lymphotactin in renal tuberculosis].

AIM: To study the expression of lymphotactin in normal kidney and renal tuberculosis and the arrangement of lymphotactin and infiltrating CD4(+) T cells and CD8(+) T cells in renal tuberculosis. METHODS: HLptn cDNA of tissues from six cases with normal kidneys and ten cases with tuberculous kidneys was amplified by RT-PCR. The RT-PCR products were separated with 2% of gel. The cDNA was cloned to vector pGM-T Easy and was completely sequenced. The immunohistochemical staining method was used to examine the expression of lymphotactin in normal kidneys and tuberculous kidneys and the expression of CD4 and CD8 in tuberculous kidneys. RESULTS: The sequence of cloned hLptn cDNA was confirmed and it was identical with the sequence of NO.U23772 published in GenBank. Both normal kidneys and tuberculous kidneys expressed hLptn mRNA. HLptn was detected not only in the cells of normal renal glomerulus and renal tubule but also in the cells of remaining renal glomerulus and renal tubule of tuberculous kidneys. The cells expressing surface antigens CD4 and CD8 scattered in granulomas. CONCLUSION: The constructive expression of hLptn is in the cells of renal glomerulus and renal tubule of normal kidney and tuberculous kidney. The accumulation of CD4(+) T cells and CD8(+) T cells in granulomas may not depend on hLptn.

Proinflammatory cytokine profile in active kidney tuberculosis patients.

INTRODUCTION: Mycobacterium tuberculosis is a facultative intracellular pathogen that developes specific T cell response expressed by the production of IL-12, IFN-gamma, and TNF-alpha. The response has been quite well investigated in the experimental models, however, there is little information about certain cytokine levels in patients with extrapulmonary tuberculosis. The shortage of data pertains also to its most common form-kidney tuberculosis, especially when bacilli dissemination into the blood circulation has occurred. OBJECTIVES: The aim of our study was to examine simultaneously the frequency of Mycobacterium tuberculosis presence in the blood circulation and the serum cytokine concentration during kidney tuberculosis to approach their relationship in the clinical infection process. It is considered that cytokine levels do not correlate with localisation of tuberculosis (pulmonary vs. extrapulmonary), however, there is little information about the cytokine levels in patients with kidney tuberculosis. MATERIALS AND METHODS: 30 patients attending the urology clinic with suspicion of kidney tuberculosis were evaluated. Serum concentrations of selected cytokines in patients with urine, urine and blood Mycobacterium tuberculosis presence were quantified by ELISA and compared to PCR negative patient and group of healthy people. RESULTS: Our study demonstrates the increase of TNF-alpha and IL-12 level in comparison to control group. TNF-alpha concentration was about 2-fold higher in the positive patients than it was in control group; IL-12 concentration was about 4-fold higher and the differences between IL-12 levels were statistically important (p < 0.05). However, no significant differences were found in IFN-gamma level among all groups. Using Spearman correlation rank test, a significant correlation was found between TNF-alpha and IL-12 in the positive patient group. The correlation factor was more significant for the group of patients with Mycobacterium tuberculosis present in blood and urine than it was in urine positive PCR group (r = -0.66 vs. r = -0.51).

[Neutrophilic and lymphocytic factors of an immune response in renal tuberculosis]. / Neitrofil'nye i limfotsitarnye faktory immunnogo otveta pri nefrotuberkuleze.

Fifty-eight patients with nephrotuberculosis at its peak were found to have a high functional activity of neutrophilic granulocytes, as determined by the lysosomal cation test, by the levels of myeloperoxidase and lactoferrin. The subpopulation of lymphocytes, concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), as well as those of IL-2 in a combination with its soluble receptor (SR-2) in the serum and supernatant of cellular cultures stimulated by phytohemagglutitin and PPD were studied. The findings suggest that there is a close correlation between the high concentrations of IL-2 and PP-alpha and the decreased content of activated lymphocytes expressing receptors to IL-2 (CD25+). Clinical remission has been ascertained to be attended only by a partial normalization of immunological parameters with antituberculous therapy.

[Combined low-intensity laser radiation in renal tuberculosis]. / Kombinirovannoe nizkointensivnoe lazernoe izluchenie pri tuberkuleze pochek.

Combined external radiation in the projection of the kidneys and intravascular laser blood radiation by applying an AZOR-2K apparatus were used in the combined treatment of 54 patients with tuberculosis of the urinary system. Analysis of the biochemical and immunological parameters of the patients' peripheral blood before and 3 weeks and 3 months after the combined treatment provided evidence suggesting a decrease in the magnitude of lipid peroxidation, an increase in the antioxidative status, and a reduction in the level of metabolites that affect on the development of the intoxication syndrome. The clinical findings suggest that the combined treatment has a beneficial impact on the course of renal tuberculosis, as appeared as better functional indices of urinary organs.

[Spectrum of tuberculosis antibodies in patients with tuberculosis and borderline urinary tract diseases]. / Spektr protivotuberkuleznykh antitel u bol'nykh tuberkulezom i pogranichnymi zabolevaniiami mochevydelitel'noi sistemy.

The spectrum of tuberculosis antibodies detectable by indirect hemagglutination test, complement consumption, passive hemaagglutilution test (PHAT), and enzyme-linked immunosorbent assay (EISA) in patients with urinary tract diseases (tuberculosis, nonspecific disorders) was studied. In untreated bacteria-isolating patients in the early phase of disease, antibodies were found in 61.8%, their different types were detectable at different rates so it is more advisable to explore responses by using several serological tests. During treatment there is an increase in antibody detection rates by ELISA. At this time only can PHAT and ELISA be made. High seropositive rates (85-100%) are ensured by PHAT and ELISA in new case in end-stage disease. The antibodies are detected in 75 of the pretreated patients with nephrotuberculosis largely by PHAT and ELISA. Examination of patients with nonspecific disease by ELISA clarifies the clinical status of these patients.

[Low-intensity laser irradiation in patients with urinary tuberculosis]. / Nizkointensivnoe lazernoe izluchenie u bol'nykh tuberkulezom mochevoi sistemy.

Combined surface radiation of renal projection area and intravascular laser radiation of blood (AZOR-2K unit) were used in combined treatment of 54 patients with urinary tuberculosis. Analysis of immunological and hematological indices of peripheral blood of patients before and after the combined treatment showed that low-intensity laser radiation activates local system of T-helpers which after specific antigenic impact differentiate into T-helpers-1. The latter synthesize in loco gamma-interferon, TNF-alpha and beta and IL-2 stimulating bactericidal mechanisms directed at destruction of M. tuberculosis and resolution of the infection focus.

Current concepts on pathogenesis of renal tuberculosis.

The pathogenesis of renal tuberculosis begins with the initial localization of the tubercle bacilli in the cortical glomeruli causing mechanical stress which lead to alteration in cell morphology, increased rate of protein synthesis and proliferation of resident glomerular cells as well as the infiltrating blood borne cells. The infection may remain localized to the renal parenchyma resulting in various forms of glomerulonephritides and/or gain access to the calyceal system causing pyelocalyceal destruction with subsequent ureteric and urinary bladder involvement. The disease may remain quiesent at the foregoing stage or progress to hydronephrosis and pyonephrosis as a result strictures and obstruction. This communication discusses the immunological responses and various specific lesions resulting from renal injury caused by mycobacterium tuberculosis.

[Immunological reactivity in tuberculosis in children]. / Immunologicheskaia reaktivnost' pri tuberkuleznoi patologii u detei.

Immunological reactivity was assessed comparatively in respiratory, intrathoracic and osteoarticular, urinary tuberculosis (122, 133, 38 children, respectively, versus 44 controls). References for age were made. The changes in immune system varied in nature, severity and relationships. Basing on these findings the author has created a complex of most informative tests in the diagnosis of childhood tuberculosis adjusted for age and site of the infection focus.

[Combined use of the Koch tuberculin provocation test and immunological tests in patients with urinary tuberculosis]. / Kompleksnoe primenenie tuberkulino-provokatsionnoi proby Kokha i immunologicheskikh testov u bol'nykh tuberkulezom mochevoi sistemy.

The use of provocative Koch test proved most effective in enhancing sensitivity of serological diagnostic tests EIA and IHA with PHA. This contributed to more accurate assessment of the tuberculous process activity in patients with advanced destruction of the kidneys. Quantitation of antituberculous antibodies may serve an additional criterium in evaluation of effectiveness of urological tuberculosis chemotherapy.

Serological response of tuberculosis patients to antigen 60 of BCG.

Two ELISA tests (IgG and IgM) for the serodiagnosis of tuberculosis, both based on antigen 60 (A60) of M. bovis BCG, were applied to 1,644 controls and patients to analyse the immune response in different forms of this infectious disease. Out of 200 healthy individuals, 148 being tuberculin--positive BCG-vaccinated adults, only 10 contacts--nurses of the pneumology department and laboratory technicians of the mycobacterial laboratory--were found positive for anti-A60 IgG. One quarter of hospitalized patients affected by non-tuberculous pneumopathies (194 in total) were found weakly positive for anti-A60 IgG. We suppose that these positive cases have suffered from inapperant infections and are in a "persistent state". Out of 344 cases of primary pulmonary tuberculosis, 88% were positive for anti-A60 IgG and 75% for the corresponding IgM. Among 97 cases of primary extra-pulmonary tuberculosis, 94% were found IgG positive and 33% IgM positive. The difference between active and inactive post-primary (chronic) tuberculosis was striking: about 100% of both pulmonary and extra-pulmonary cases (367 altogether) had high titers of anti-A60 IgG but IgM positivity was observed in only 15% of the cases, whereas in inactive and quiescent noncavitary tuberculosis (442 cases), 57% of the patients were weakly positive for anti-A60 IgG and none were positive for IgM. Kinetics of synthesis of anti-A60 IgG and IgM were analysed in primary and post-primary (chronic) active tuberculosis. The IgM tracing immune response to A60 was shorter and lower during primary tuberculosis as compared to post-primary tuberculosis. Our findings point to the high prognostic value of the A60- ELISA test for tuberculosis. Anti-A60 IgM mark initial stages of the disease or reactivation processes whereas anti-A60 IgG last longer than IgM and provide an evaluation of the intensity of the infectious process. Repeated serological tests allow monitoring of the course of the infection and the efficacy of therapy. The test is negative in healthy BCG-vaccinated persons (tuberculin-positive) and healed tuberculous infection cases. The combined use of both IgG and IgM tests helps in the correct diagnosis of "false positive" cases.

[Immunomodulation in patients with cavernous kidney tuberculosis using piperazine adipinate and amniocene]. / Immunokorrektsiia u bol'nykh kavernoznym tuberkulezom pochek piperazina adipinatom i amniotsenom.

Findings of a complex immunologic examination of 138 patients with active cavernous tuberculosis of the kidneys concurrent with secondary immunodeficiency are presented. Biostimulators and immunomodulating drugs were administered as conservative treatment in this case. Changes in cellular and humoral immunity indices as well as those of the mononuclear-phagocyte system before and after treatment were traced in the groups of patients receiving biogenic stimulators (such, as aloe extract, vitreous body, plasmol, Fibs) and immunoregulating drugs (like piperazine adipinate and injected amniocene). It was found that the biogenic stimulators fail to have a pronounced effect on the immunologic indices. The inclusion of piperazine adipinate and injected amniocene into a complex of antibiotic and chemotherapy brings about a significant improvement of the cellular immunity indices and the mononuclear-phagocyte system function which are inhibited to a greater extent in patients with active destructive nephrophthisis. A recommended use of piperazine adipinate and amniocene as adjuncts to a complex treatment has been proved in patients of this category by means of clinicoimmunologic correlations.

[Effect of terrilytin on tissue bacteriostatic activity in the chemotherapy of renal and female genital tuberculosis in an experiment]. / Vliianie terrilitina na bakteriostaticheskuiu aktivnost' tkanei pri khimioterapii tuberkuleza pochek i zhenskikh polovykh organov v éksperimente.

The effect of terrilytin on the bacteriostatic activity of the tissues (BAT) under conditions of antibacterial therapy was studied on experimental models of tuberculosis of the kidneys and female genitalia in 46 rabbits. It was shown statistically that terrilytin promoted an increase in the BAT and might be used as an agent increasing the effect of antibacterial therapy of tuberculosis. The level of the increase of the BAT depended on its initial level which was inversely proportional to the level of the lesions. At the same time the effect of terrilytin was directly proportional to the level of these lesions unfavourable for the drug penetration into the tissues and tuberculous foci. The results of the study are promising in increasing the efficacy of antibacterial therapy of extrapulmonary tuberculosis of the above localizations by the use of terrilytin.