| Background and ObjectiveTuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M.TB). In recent years, because of the increasing of environmental pollution, and incidence of diabetes, as well as the AIDS epidemic, the incidence rate of tuberculosis rises again, which has become a serious hazard to human health in global.Since the mid-80s, the incidence rate of tuberculosis has been rising, in which immune function disorders are one of the reasons. M.TB can damage any parts of the body, especially attack the lungs, but the local cellular immune mechanism in tuberculosis is still to be clarified. In recent years, the study of the immune response to tuberculosis never ceased, it is an important significance to control the infection from the body itself. A large number of clinical data and animal experiments show that the general person infected by M.TB is not, but about 5 ~ 10% of those infected when their immunity declines, then develop to clinical TB by the rate of 10%. So the occurrence and development of tuberculosis is the result of the interaction between M.TB and the host, which is closely related to the body's immune state. In recent years, people in the study about cellular immune mechanisms of TB recognized more and more that: in the disease, many cytokines involved in the immune response and immune pathology in incidence and development of tuberculosis. In which IL-4, TNF-α, IFN-γ, TGF-βare closely related to tuberculosis, Immune etiology study about tuberculosis had shown that proliferation, liquefaction, and necrosis of tuberculosis lesions are the direct causes of the deterioration, even death. So TB is also a consequence of immune disorders. The conventional chemotherapy drugs can only kill M.TB, but can not correct abnormalities of the immune pathogenic response, so if we adjuste the abnormalities of immune pathogenic to a normal state, there will be a vital significance to the success of chemotherapy and eliminate the source of infection. At present, some cytokines have been used to the clinic, such as IFN-γagents, TNF-αinhibitors, and their practical application has been awared. But so far there is no clear clinical guidance for local cytokine therapy.TB is one of infectious diseases, which is closely related to immune response. And in the process the cellular immune responses are dominant. Cellular immune response is mediated by T lymphocytes, macrophages as effector cells, and a variety of cytokines constitute the immune network which attend to the TB immune response and immune pathogenesis. Now the majority of scholars think that the levels of TNF-α, IL-4, IFN-γ, TGF-βare closely related to the severity, activity, prognosis of tuberculosis. Our study was based on related tuberculosis immune research, compared to themselves, explored the related cytokines levels in the bellows and the peripheral blood cells (PBC), and their relationship with each other, and the relationship between the cytokines in bellows and the number of M. tuberculosis bacilli in sputum, and their change in the process of treatment. Our study was to provide evidences for cytokine therapy.Methods33 cases of tuberculosis patients, who met the standard of diagnosis, were randomly selected from September 2009 to December 2009 in Guangzhou Chest Hospital. The specimens of sputum and blood were collected at before and after treatment. Record their clinical and laboratory data, such as gender, age, diagnosis, sputum examination, chest-X-ray and so on. The IL-4, TNF-α, TGF-β, IFN-γlevels were measured by ELISA. The smears of sputum were stained by the Wright's method and the acid-fast method, and then the sputum samples were tested for cell and the number of M. tuberculosis bacilli by optical microscope. Results1. Before treatment the sputum supernatant IL-4, TNF-α, TGF-β, IFN-γlevels which were (140.73±83.23)pg/ml, (463.90±268.22)pg/ml, (6482.21±3670.54)pg/ml, (118.90±96.24)pg/ml were significantly higher than their serum levels which were (48.60±18.60)pg/ml, (145.06±48.55)pg/ml, (181.63±118.73)pg/ml, (16.51±10.79)pg/ml, the difference was statistically significant (P<0.05). In which the sputum supernatant IL-4 level was 3.68 times than the serum level, the sputum supernatant TNF-αlevel was 4.03 times than the serum level, the sputum supernatant IFN-γlevel was 12.40 times than the serum level, the sputum supernatant TGF-βlevel was 65.02 times than the serum level.2. Before treatment the sputum supernatant IL-4 and TNF-αlevels were the linear positive correlation, there is statistical significance (P<0.05); And the level of IFN-γhad no significant correlation with the levels of IL-4, TNF-αand TGF-βin sputum supernatants (P>0.05); And the level of TGF-βhad no significant correlation with the levels of IL-4, TNF-αin sputum supernatants (P>0.05), too.3. Before treatment the levels of IL-4 and TNF-αin serum had no significant correlation (P>0.05); The levels of TGF-βand IFN-γin serum were the linear positive correlation, there is statistical significance(P<0.05); And the level of IL-4 had no significant correlation with the levels of IFN-γ, TGF-βin serum (P>0.05); And the level of TNF-αhad no significant correlation with the levels of TGF-β, IFN-γin serum (P>0.05).4. In patients with number of M.TB in sputum the sputum supernatants IL-4, TNF-α, TGF-β, IFN-γlevels had significant difference, from the view of average level of cytokine and clinic, with the increasing of the number of M.TB in sputum the secretion of the related cytokines increased in varying degrees, but there were not statistically significant (P>0.05); But their serum levels were no correlation with the number of M.TB in sputum, there is no significant difference (P>0.05).5. Pre-treatment the sputum supernatant IL-4, TNF-α, TGF-β, IFN-γlevels which were (140.73±83.23) pg/ml, (463.90±268.22) pg/ml, (6482.21±3670.54) pg/ml, (118.90±96.24) pg/ml in patients with non-cavitary TB were different to those in patients with cavitary TB which were (200.99±191.67) pg/ml, (560.22±399.89) pg/ml, (8610.79±4301.39) pg/ml, (164.96±119.34) pg/ml, but there was not statistically significant(P>0.05). However, from the view of the clinic and the average level of cytokines, the levels of related cytokines in patients with cavitary pulmonary tuberculosis were increased more than that in non-cavitary in varying degrees.6. No difference was found in the serum IL-4, TNF-α, TGF-β, IFN-γlevels between non-cavitary TB group in which the levels were (47.41±14.45)pg/ml, (145.19±58.30)pg/ml, (175.47±122.35)pg/ml, (15.95±11.12)pg/ml and cavitary TB group in which the levels were (49.71±22.20)pg/ml, (144.93±39.10)pg/ml, (187.43±118.69)pg/ml, (17.04±10.79)pg/ml, there were not statistically significant (P>0.05).7. Pre-treatment compared the ratio of IL-4, TNF-α, TGF-β, IFN-γin sputum supernatant and those in serum in patients with non-cavitary TB which were (2.87±1.65), (3.50±2.30), (57.73±51.19), (12.26±13.08) to cavitary TB patients which were (4.45±4.16), (4.52±4.08), (71.89±57.89), (12.55±10.66), they had significant difference, but there were not statistically significant(P>0.05). However, from the view of the clinic and the average level of cytokines, the ratio of related cytokines in patients with cavitary pulmonary tuberculosis were higher than non-cavitary in varying degrees.8. After 2 weeks of treatment the levels of IL-4, TNF-α, TGF-β, IFN-γwhich were (191.89±126.89)pg/ml, (498.35±374.92)pg/ml, (6939.69±5008.63)pg/ml, (145.73±75.21)pg/ml in sputum supernatant were no significant changes compared to pre-treatment, there were no statistical difference (P>0.05).9. After 2 weeks of treatment the levels of IL-4 and TNF-αin sputum supernatant patients with pulmonary tuberculosis showed a linear positive correlation (P<0.05), there was statistical difference; The levels of TGF-βand TNF-αin sputum supernatants showed a linear positive correlation (P<0.05), there was a significant difference; While the levels of IFN-γand IL-4, TNF-α, TGF-βin sputum supernatant were no significantly correlation (P>0.05); The levels of TGF-βand IL-4 in sputum supernatant had no significant correlation (P>0.05).10. After 2 weeks of treatment in patients with pulmonary tuberculosis the levels of△IL-4 and△TNF-αin sputum supernatant showed a linear positive correlation, there is a significant difference(P<0.05); But the levels of△IFN-γand△IL-4,△TNF-α,△TGF-βin sputum supernatants were no significant correlation (P>0.05), and the levels of△TGF-βand△IL-4,△TNF–αin sputum supernatants had no significant correlation (P>0.05).11. After 2 weeks of treatment IL-4/TNF-αratio (0.49±0.33) was higher when compared to pre-treatment (0.31±0.21), there were statistically significant (P<0.05). But no different was found in the IL-4/IFN-γratio between after treament (1.79±1.94) and before treatment (2.58±4.49), they had no statistical significance (P>0.05).Conclusion1. The levels of IL-4, TNF-α, TGF-β, IFN-γin localized lesions of tuberculosis were higher significantly than those in serum; In which the sputum supernatant IL-4 level was 3.68 times than the serum level, the sputum supernatant TNF-αlevel was 4.03 times than the serum level, the sputum supernatant IFN-γlevel was 12.40 times than the serum level, the sputum supernatant TGF-βlevel was 65.02 times than the serum level.2. With the increasing of the number of M.TB in sputum, the secretion of the related cytokines increased in varying degrees, but in serum they were no correlation with the number of M.TB in sputum.3. The levels of related cytokines in sputum supernatant in patients with the cavitary PTB were higher than those in non-cavity pulmonary tuberculosis in varying degrees, but in serum there was no statistically significant; The ratio of sputum supernatant IL-4, TNF-α, IFN-γ, TGF-βlevels and serum cytokines levels in patients with cavitary PTB are higher than that with non-cavity PTB in varying degrees.4. 2 weeks after treatment the sputum supernatant IL-4 and TNF-αlevel were linear positive correlation, but in serum they had no significant correlation. 5. Post-treatment IL-4/TNF-αratio is obviously increased, and may be used as a master of treatment evaluation. But IL-4/IFN-γratio is no change between before and after treatment.
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