Effect of oral supplementation with branched-chain amino acid granules on serum albumin level in the early stage of cirrhosis: a randomized pilot trial

We designed a randomized pilot trial to examine whether increase or preservation of serum albumin levels was attained with earlier administration of branched-chain amino acid (BCAA) granules for cirrhosis in grade A according to Child–Pugh classification using branched-chain tyrosine ratio (BTR) as an indicator. Forty patients with HCV-related cirrhosis in grade A with serum albumin level between 3.5 and 3.9 g/dl were enrolled in this study. Half of the patients were randomly assigned to receive 14.3 g/day of BCAA granules orally, and half were assigned to a control. Patients were evaluated at entry and at 1-year interval for at least 2 years. For patients whose BTR was less than 4.0, mean change in serum albumin in the BCAA group was significantly higher than that in the control group after 1 and 2 years of treatment. However, for patients whose BTR was more than 4.0, mean change in serum albumin in the BCAA group was not significantly higher than that in the control group after 1 and 2 years of treatment. In conclusion, early oral supplementation of BCAA for HCV-related cirrhosis with serum albumin level between 3.5 and 3.9 g/dl and BTR less than 4.0, improves serum albumin levels and thus might improve prognosis.     

A study on relation between active pulmonary tuberculosis and underlying diseases]

A study was made on the relation between active pulmonary tuberculosis and underlying diseases in 119 tuberculosis patients. Out of total 119 patients, 87 patients (73.1%) had underlying diseases. The most common underlying disease was diabetes mellitus in 34 patients (39.1%), followed by HCV (+) chronic hepatitis, sequela of cerebral infarction, hypertension and gastric ulcer. In patients who had underlying diseases, the mean age was higher, proportion of sputum smear positive cases was higher, albumin was lower, and period until sputum culture negative conversion was longer. In patients who had diabetes mellitus, proportion of cases with cavity on chest X-P was higher, and in patients who had sequela of cerebral infarction or hypertension, mean age was higher. In patients who had diabetes mellitus and whose HbA1C was > or = 9%, proportion of smear positive cases was higher, albumin was lower and period until culture negative conversion was longer than in patients who had diabetes mellitus and whose HbA1c was < 9%, suggesting that control of blood sugar in diabetes mellitus related to severity of pulmonary tuberculosis. In patients who had diabetes mellitus and whose albumin was < 3 g/dl, period until culture negative conversion was longer than in patients who had diabetes mellitus and whose albumin was > or = 3 g/dl. In patients who had underlying diseases, these diseases caused decline of tuberculous immunity and nutritional disturbance represented by lower albumin also promoted decline of tuberculous immunity. It is suggested that the underlying diseases affected the onset and progression of pulmonary tuberculosis.     

Soluble interleukin-2 receptor levels in patients with pulmonary tuberculosis

Utilizing an enzyme-linked immunosorbent assay, we detected markedly elevated serum levels of soluble interleukin-2 (IL-2) receptors in patients with untreated pulmonary tuberculosis. In these patients, we also found that serum levels of soluble IL-2 receptors were closely correlated with serum adenosine deaminase levels (r = 0.869, p less than 0.001). Therefore, serum soluble IL-2 receptors appear to reflect the existence of active cell-mediated immunity in pulmonary tuberculosis and may prove to be a useful immunological marker for pulmonary tuberculosis.     

Inhibitory effect of branched-chain amino acid granules on progression of compensated liver cirrhosis due to hepatitis C virus

Background. A phase II randomized controlled trial was conducted in patients with compensated liver cirrhosis to investigate the inhibitory effect of branchedchain amino acid (BCAA) granules for oral use (TK-98) on disease progression. Methods. Patients who had compensated liver cirrhosis due to hepatitis C virus with baseline serum albumin levels between 3.6 and 4.5 g/dl were assigned to the TK-98 group, which was treated with BCAA granules (TK-98) for 168 weeks, or to a control group (no treatment). Results. No symptoms indicating decompensated cirrhosis, including ascites, edema, and hepatic encephalopathy were reported in either the TK-98 or control group during the study observation period. Hepatocellular carcinoma (HCC) was noted in eight of the 39 patients studied, and of these three received TK-98 (15.8%) and five were untreated (25.0%). A time-to-event analysis for the effect of BCAA therapy on development of HCC revealed no statistically significant differences between the two groups. However, an additional analysis of data from a subgroup with a baseline serum albumin level of <4.0 g/dl showed that the incidence of HCC was likely to be lower in BCAA-treated patients. Conclusions. BCAA may inhibit hepatic carcinogenesis in patients with compensated cirrhosis with a serum albumin level of <4.0 g/dl.     

A study of causes of death among patients with active pulmonary tuberculosis from the standpoint of host factors

To clarify the clinical features of fatal cases of active pulmonary tuberculosis, 36 patients with sputum positive for tubercle bacilli on admission were examined retrospectively. They were divided into two groups, those who died of tuberculosis (Group I), and those who died of non-tuberculous diseases (Group II). The mean age of all the patients was 74.8 years, and the male: female ratio was 7 : 3. In Group I (n = 26), the direct causes of death were respiratory failure (35%), general weakness (27%) and acute progression of tuberculosis (31%), and in Group II (n = 10), about half of the patients died of neoplasms. In addition, a control group (Group III) (n = 27) of patients matched for age and sex with Group I, was examined. They were tuberculous patients who had improved and were subsequently discharged after chemotherapy. Compared with Group III, more patients in Group I showed poor oral feeding and had been bedridden on admission. Their nutritional status was significantly poorer, based on determination of total serum protein, albumin, total serum cholesterol, and hemoglobin. With respect to cell-mediated immunity, Group I patients showed significantly lower peripheral lymphocyte counts and a reduced PPD skin reaction. However, the disease was more serious in Group I than in the control. It was suggested that patients subsequently died of active pulmonary tuberculosis showed not only serious illness, but also malnutrition and depressed cell-mediated immunity.     

The Incidence of Diarrhea in Patients with hypoalbuminemia Due to Acute or Chronic Malnutrition during Enteral Feeding

Objectives: Critically ill patients usually have hypoalbuminemia. The incidence of diarrhea in patients with hypoalbuminemia receiving enteral nutrition was studied. Methods: One hundred and ninety-eight patients with serum albumin level below 3 g/dl in the Burn Unit and Nutritional Support Service were retrospectively studied. Diarrhea was defined as liquid or loose stool at least three times a day with a daily volume of more than 300 g for at least 2 days. Most patients in the Burn Unit had acute or subacute onset of hypoalbuminemia, and most patients who were referred to the Nutritional Support Service had a chronic onset of hypoalbuminemia. The patients whose diarrhea were due to formula-related factors, administration techniques, or concomitant drug therapy were excluded. Results: The results showed that 27% of the patients with albumin levels less than 2 g/dl had diarrhea, but only 10.5% of patients with albumin levels higher than 2 g/dl had diarrhea; the difference was significant. Diarrhea occurred in 35.1% of the patients with chronic development of hypoalbuminemia, but only 9.9% of the patients with rapid development of hypoalbuminemia had diarrhea; that difference also was significant. Conclusions: We concluded that the hypoalbuminemia-related diarrhea during tuhe feeding was significantly higher in patients with albumin levels less than 2 g/dl, and the patients with hypoalbuminemia due to chronic malnutrition had a significantly higher incidence of diarrhea than those with acute malnutrition, such as hurned patients.     

Defective interleukin-2 production and interleukin-2 receptor expression in pulmonary tuberculosis

The evolution of Mycobacterium tuberculosis as an intracellular pathogen has led to a complex relationship between it and its host, the human mononuclear phagocyte. The products of M. tuberculosis-specific T lymphocytes are essential for macrophage activation for intracellular mycobacterial killing. However, dysfunction cell-mediated immune response to infection with M. tuberculosis may contribute to progressive primary infection or reactivation of endogenous foci of mycobacteria. Th1 cells produce IL-2, which is essential for proper cellular immunity. The aim of this study was to identify the variation in IL-2 activity and soluble IL-2 receptor (IL-2 R) in peripheral blood lymphocyte in patients suffering with pulmonary tuberculosis. A significant decrease in IL-2 and IL-2 receptor level was observed in patients with pulmonary tuberculosis when compared to normal controls. Our results suggested that patients with pulmonary tuberculosis had a defect in IL-2 production. Better understanding of these interactions will allow the development of increasingly specific immune-based interventions for prevention and treatment of tuberculosis.     

Evaluation of the effects of combination therapy with branched-chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis

Aim: Disorders of protein metabolism in liver cirrhosis can affect prognosis or cause complications. Treatment with branched-chain amino acid (BCAA) and zinc supplements has been shown to be effective against abnormal nitrogen metabolism in liver cirrhosis. There are, however, few studies on the effects of combining these supplements. In this study, the effect of combining BCAA and zinc treatment in cirrhosis was investigated. Methods: Forty patients with liver cirrhosis who had blood albumin levels of 3.5 g/dL or less and blood zinc levels of 70 mug/dL or less were randomized to receive either BCAA alone or a combination of BCAA and zinc supplements. Blood albumin, the Fischer ratio, and ammonia levels were compared over 5-6 months of treatment. Results: In the combination group, the post/pre treatment change ratio in blood ammonia levels decreased significantly (0.87 +/- 0.26 vs. 1.22 +/- 0.38, P = 0.0033), and the change ratio in the Fischer ratio increased significantly (1.22 +/- 0.29 vs. 1.08 +/- 0.16, P = 0.0165) in comparison with the BCAA monotherapy group. The change ratio in blood albumin levels showed no significant difference between the groups (1.01 +/- 0.07 vs. 1.03 +/- 0.08, P = 0.4646). Conclusions: More improvement in disorders of nitrogen metabolism in liver cirrhosis occurred after administration of BCAA with zinc than after BCAA alone over 5-6 months of treatment. Further investigation is necessary to determine mechanisms of the action and longer-term clinical efficacy.     

Nutritional assessment of chronic pulmonary emphysema and the significant relation of malnutrition to pulmonary function and respiratory muscle function

We assessed nutritional status in 30 patients with pulmonary emphysema and 60 healthy controls. The relationship between nutritional status, pulmonary function and respiratory muscle function was also studied. Anthropometric measures, visceral proteins such as PA and RPB, and the Fischer ratio (BCAA/AAA), an index of imbalance of amino acids were significantly lower in the patients. The incidence of moderately malnourished patients with less than 80% of IBW was 40%. The incidence of hyporetinol-binding protein was 40%. 48% of the patients were found to show an amino acid imbalance. These findings suggested that protein-energy malnutrition in association with amino acid imbalance occurred commonly in patients with pulmonary emphysema. FEV1% correlated significantly with some anthropometric indices and the Fischer ratio. Respiratory muscle function, assessed by P1 max, correlated significantly with some anthropometric indices and grasp strength. These results suggested that the degree of airway obstruction and respiratory muscle function was associated with malnutrition characterized by the reduction of the Fischer ratio.     

应用NRS2002方法对肺结核合并肺部感染患者的营养风险筛查和分析

目的研究肺结核合并肺部感染患者的营养风险、营养不足发生率,并与单纯肺结核患者进行比较。方法采用NRS2002营养风险筛查方法,随机选择2012年4月~10月新入院肺结核患者200例,在入院2天内和住院2周时进行营养风险筛查初查和复查,并按是否合并肺部感染,分为研究组(90例)和对照组(110例),比较两组营养不足、营养风险的发生率,进行统计分析。营养不足判定标准为体重指数BMI18.5kg/m2、血清白蛋白sALB30 g/L。结果总的营养风险和营养不足发生率分别为82%(164/200)和43.5%(87/200)。刚入院时研究组的营养风险发生率(88.9%)比对照组高(76.4%),P0.05;治疗2周后复查,两组的营养风险发生率明显降低,P值均0.01,研究组(53.3%)仍然明显高于对照组(39.1%),P0.05;营养不足率组间及组内比较均无明显差别,P值均0.05。结论肺结核合并肺部感染住院患者的营养风险和营养不足发生率较高,应推广和使用NRS2002营养风险筛查方法,作为临床实施营养支持的参考依据。     

Interaction between interleukin-1 and tumor necrosis factor productions by peripheral blood monocytes and nutritional disturbance in active pulmonary tuberculosis

Malnutrition is frequently observed in patients with pulmonary tuberculosis. We have already reported the nutritional disturbance in those patients by comprehensive nutritional assessment. But the mechanism of this nutritional disturbance remains unclear. We anticipated that cytokines contributed to the nutritional disturbance. To elucidate this mechanism we measured the productions of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood monocytes, and correlated them with nutritional parameters in those patients. These cytokines had been reported to mediate metabolic alterations in inflammatory process. Subjects were 45 patients with bacteriologically confirmed pulmonary tuberculosis and their controls matched by age and sex. Adherent monocyte at 0.5 x 10(6)/ml were stimulated by lipopolysaccharide (LPS), and the culture supernatant was measured by ELISA for IL-1 and TNF. In order to assess nutritional status we measured serum albumin, transferrin, prealbumin, retinol binding protein, branched chain amino acid (BCAA)/aromatic amino acid (AAA) ratio as amino acid imbalance index, % ideal body weight (%IBW), % arm muscle circumference (% AMC) as muscle mass index, % triceps skin fold thickness (% TSF), as fat store index. The results were as follows: (1) Patients with active pulmonary tuberculosis were confirmed to be malnourished in visceral proteins, plasma amino acid, and anthropometric indices. (2) In patients with moderate or mild nutritional depletion the production of IL-1 and TNF was higher than that in healthy controls, and significantly correlated inversely with the nutritional parameters. (3) In patients with severe nutritional depletion the production of IL-1 and TNF was lower than that in healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early administration of branched-chain amino acid granules

The effect of malnutrition on survival in patients with decompensated liver cirrhosis has not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increase serum albumin concentration in patients with decompensated cirrhosis but its effects on survival are unclear. The BCAA to tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between 4.41 and 10.05, and a Fischer's ratio of 1.8 corresponds to a BTR of 3.5) in patients with decompensated liver cirrhosis, and BCAA inhibits hepatic carcinogenesis in patients with compensated cirrhosis. This review discusses data regarding the effect of early administration of BCAA granules based on the ratio of BCAA to BTR on prognosis in patients with cirrhosis.     

Restoration of innate host defense responses by oral supplementation of branched-chain amino acids in decompensated cirrhotic patients

Aim: It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. The aim of the present study was to examine the effects of oral supplementation of branched-chain amino acids (BCAA) on host defense mechanisms in peripheral blood of patients with decompensated cirrhosis. Methods: Ten patients with decompensated cirrhosis received 12 g BCAA daily for 3 months. Phagocytic function of neutrophils and NK activity of lymphocytes as well as serum albumin levels and Fisher's ratios were determined before and at 1 and 3 months of BCAA supplementation. For quantification of phagocytic function, fluorescent intensities of cells in the neutrophil region in the cytogram were determined by flow cytometry after incubation of whole blood with fluorescent microspheres. NK activity was estimated by (51)Cr release assay using K-562 cell line as target cells. Results: Phagocytic function of neutrophils was significantly improved by 3-month BCAA supplementation (P < 0.01). Thechanges of NK activity were also significant at 3 months of supplementation compared with before supplementation (P < 0.01). Fisher's ratios were significantly increased at 3 months of BCAA supplementation compared with those before oral supplementation (P < 0.05), although the changes of serum albumin level were not statistically significant. Conclusions: BCAA oral supplementation improved phagocytic function of neutrophils and NK activity of lymphocytes in cirrhotic patients. BCAA supplementation may reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis.     

Serum Albumin Level and Risk for Mortality and Hospitalization in Adolescents on Hemodialysis

Background and objectives: National Kidney Foundation Dialysis Outcomes Quality Initiative practice guidelines recommend serum albumin ≥4.0 g/dl for adults who are on hemodialysis. There is no established pediatric target for albumin and little evidence to support use of adult guidelines. This study examined the association between albumin and risk for death and hospitalization in adolescents who are on hemodialysis.Design, setting, participants, & measurements: This retrospective cohort study linked data on patients aged 12 to 18 yr in 1999 and 2000 from the Centers for Medicare and Medicaid Services’ End Stage Renal Disease Clinical Performance Measures Project with 4-yr hospitalization and mortality records in the United States Renal Data System. Albumin was categorized as <3.5/3.2, ≥3.5/3.2 and <4.0/3.7, and ≥4.0/3.7 g/dl.Results: Of 675 adolescents, 557 were hospitalized and 50 died. Albumin ≥4.0/3.7 g/dl was associated with male gender, Hispanic ethnicity, and higher hemoglobin level. Those with albumin ≥4.0/3.7 g/dl had fewer deaths per 100 patient-years and fewer hospitalizations per time at risk. In multivariate analysis, patients with albumin ≥4.0/3.7 g/dl had 57% decreased risk for death. Poisson regression showed progressive decrease in hospitalization risk as albumin level increased; however, confidence intervals were similar between albumin ≥4.0/3.7 g/dl and albumin ≥3.5/3.2 and <4.0/3.7 g/dl.Conclusions: This study demonstrates decreased mortality and hospitalization risk with albumin ≥3.5/3.2 g/dl and suggests that adolescent hemodialysis patients who are able to achieve serum albumin ≥4.0/3.7 g/dl may have the lowest mortality risk.The National Kidney Foundation Dialysis Outcomes Quality Initiative (DOQI) practice guidelines were first established in 1997 to create standards for dialysis care. The current outcome goal for serum albumin for adult maintenance dialysis patients is a predialysis or stabilized serum albumin equal to or greater than the lower limit of the normal range (4.0 g/dl for the bromcresol green [BCG] laboratory method) (1). There is no established pediatric outcome goal for serum albumin. For adults who are on hemodialysis (HD), serum albumin <4.0 g/dl has been shown to be a strong predictor of mortality (2–4). For children, serum albumin level <3.5/3.2 g/dl (BCG/bromcresol purple [BCP]) is generally considered the cutoff for hypoalbuminemia, although normal values for children 5 to 19 yr of age are serum albumin 4.0 to 5.3 g/dl (5). There is very little evidence to assess the relevance of adult target serum albumin levels in pediatric patients with ESRD.     

CD4＋T淋巴细胞对肺结核患者血清白蛋白的影响

目的 探讨外周血CD4⁺ T淋巴细胞对肺结核患者血清白蛋白的影响。 方法 对119例初治肺结核患者进行淋巴细胞亚群和血清白蛋白测定,探讨细胞免疫功能与血清白蛋白相关性;同时,根据其CD4⁺ T淋巴细胞亚群水平,分为免疫低下组62例和正常组57例,探讨细胞免疫功能低下对低蛋白血症的影响。 结果 （1）所有纳入患者外周血CD4⁺ T淋巴细胞［（516.6±266.1）×10⁹/L］与CD3⁺ T淋巴细胞［（841.6±398.8）×10⁹/L］、CD8⁺ T淋巴细胞［（261.0±142.6）×10⁹/L］、CD4⁺/CD8⁺ T淋巴细胞比值（2.33±1.40）呈正相关（分别为r=0.883,P=0.000;r=0.579,P=0.000;r=0.365,P=0.000）。（2）外周血CD4⁺T淋巴细胞与血清白蛋白呈正相关（r=0.116,P=0.033）。（3）在免疫低下组中,肺部病灶范围达4个肺野以上者43例（占69.4%）,明显高于正常组的22例（占38.6%）,差异有统计学意义（χ²=11.335,P=0.001）;免疫低下组治疗前血清白蛋白［（33.9±5.5）g/L］明显低于正常组［（36.1±5.7）g/L］（t=2.187,P=0.031）。 结论 在肺结核患者中CD4⁺ T淋巴细胞与治疗前血清白蛋白水平呈正相关。CD4⁺ T淋巴细胞低下肺结核患者,其病灶范围较广,容易并发低蛋白血症。     

Supplementation with Alfacalcidol increases protein intake and serum albumin concentration in patients undergoing hemodialysis with hpoalbumineamia

BACKGROUND: We have reported that vitamin D deficiency may be implicated in the pathogenesis of hypoalbuminemia observed in patients with end-stage renal disease, but the mechanism remains to be clarified. The aim of the present study was to determine whether supplementation with alfacalcidol might increase protein intake in hemodialyzed patients with hypoalbuminemia. METHODS: Twelve patients with hypoalbuminemia under 3.5 g/dl undergoing maintenance hemodialysis and not taking active forms of vitamin D were orally supplemented with 0.5 microg of alfacalcidol daily for 8 weeks. Normalized protein catabolic rate (nPCR), an index of protein intake, and serum concentrations of albumin, interleukin-6 (IL-6), IL-1beta, and soluble tumor necrosis factor-alpha receptor-II (sTNFR-II), an index of tumor necrosis factor-alpha activity, were determined before and after supplementation with alfacalcidol. RESULTS: Supplementation with alfacalcidol increased nPCR from 0.96 +/- 0.20 to 1.16 +/- 0.15 g/kg/day (p < 0.005), thereby increasing serum albumin concentration from a baseline of 3.13 +/- 0.35 to 3.32 +/- 0.29 g/dl (p < 0.05). The baseline serum concentrations of sTNFR-II and IL-6 were markedly elevated, whereas those of IL-1beta were under the detection limit. Supplementation with alfacalcidol significantly decreased serum concentration of sTNFR-II from 23.8 +/- 4.38 to 19.7 +/- 3.93 ng/ml (p < 0.001) but did not alter serum IL-6 concentration. CONCLUSION: Supplementation with alfacalcidol can increase protein intake and serum albumin concentration in hemodialyzed patients with hypoalbuminemia, probably through the suppressed tumor necrosis factor activity.     

Branched-chain amino acid treatment before transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM: To examine the significance of branched-chain amino acid (BCAA) treatment before transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).METHODS: This study included 99 patients who underwent TACE therapy for HCC at our hospital and were followed up without treatment for at least 6 mo between January 2004 and January 2010. They were divided into 2 groups: those receiving BCAA granules (n = 40) or regular diet (n = 59, control). Data obtained were retrospectively analyzed (prior to TACE, and 1 wk, 1, 3, and 6 mo after TACE) in terms of nutritional condition and clinical laboratory parameters (serum albumin level and Child-Pugh score), both of which are determinants of hepatic functional reserve.RESULTS: The BCAA group comprised 27 males and 13 females with a mean age of 69.9 ± 8.8 years. The patients of the BCAA group were classified as follows: Child-Pugh A/B/C in 22/15/3 patients, and Stage II/III/IVA HCC in 12/23/5 patients, respectively. The control group comprised 32 males and 27 females with a mean age of 73.2 ± 10.1 years. In the control group, 9 patients had chronic hepatitis, Child-Pugh A/B/C in 39/10/1 patients, and StageI/II/III/IVA HCC in 1/11/35/12 patients, respectively. Overall, both serum albumin level and Child-Pugh score improved significantly in the BCAA group as compared with the control 3 and 6 mo after TACE (P < 0.05). Further analysis was performed by the following categorization: (1) child-Pugh classification; (2) liver cirrhosis subgroup with a serum albumin level > 3.5 g/dL; and (3) epirubicin dose. A similar trend indicating a significant improvement of all variables in the BCAA group was noted (P < 0.05).CONCLUSION: Treatment with BCAA granules in patients who have undergone TACE for HCC is considered useful to maintain their hepatic functional reserve.     

Interleukin-2 (IL-2) in active pulmonary tuberculosis]

To clarify the precise of cellular immunity mechanism in pulmonary tuberculosis, we investigated the amount of IL-2 in patients with untreated active pulmonary tuberculosis. When serum adenosine deaminase (ADA) activity was examined using enzyme assay, an abnormally high level was observed in all patients (29.0 + 11.6 IU/ml, mean + SD; 4.5-17.8, normal range). Likewise, the level of serum-soluble interleukin-2 receptor (IL-2R) measured by ELISA showed abnormal high level in all patients (844.3 + 584.8 IU/ml; 80-300, normal range). When stimulated using PHA, the peripheral lymphocyte's ability to produce IL-2 revealed no difference between control subjects and patients. It was, however, noted that the lymphocytes of the patients significantly suppressed IL-2 responsiveness when compared to the control subjects (P less than 0.05). The serum IL-2 concentration measured using RIA could not be detected in any of the patients as was the same for control subject. All of the above mentioned results suggest that T-cell activation which caused increment in serum ADA activity and soluble IL-2R occurred in active pulmonary tuberculosis. The suppressed IL-2 responsiveness in the peripheral lymphocytes of patients proposes the possibility of soluble IL-2R reduction by the negative feedback mechanism in IL-2-sensitive lymphocytes.     

Reduced NK activity in pulmonary tuberculosis patients with/without HIV infection: identifying the defective stage and studying the effect of interleukins on NK activity.

SETTING: A study was undertaken to understand the non-major histocompatibility restricted cytotoxicity in order to delineate the role of natural killer (NK) cells towards the development of host immunity to tuberculosis. OBJECTIVE: (a) Enumeration of NK cell numbers and activity in normal individuals (35), pulmonary tuberculosis patients (32), HIV-infected TB patients (20) and patient contacts (10), (b) effect of treatment on NK status, (c) enumeration of effector-target conjugates and (d) effect of in vitro cytokine stimulation on NK activity. DESIGN: NK cells were enumerated by flow cytometry. NK activity was assessed by chromium release assay before and after treatment for tuberculosis and after stimulation with IL-2/IL-12. Novel flow cytometric method was standardized to enumerate effector-target conjugates. RESULTS: No changes were seen between different groups as far as number of NK cells and relative proportions of different conjugate types were concerned, but there was a decrease in NK activity in TB patients which increased after treatment. Augmentation of NK activity was observed after cytokine stimulation. CONCLUSION: Lowered NK activity during tuberculosis infection is probably the 'effect' and not the 'cause' for the disease as demonstrated by the follow-up study. Similar number of conjugates in both groups indicates no defect in the recognition/binding step but probably at subsequent steps of the cytotoxic process. Augmentation of NK activity with cytokines implicates them as potential adjuncts to tuberculosis chemotherapy.