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Paradoxical reactions (PRs) to antituberculosis (anti-TB) drugs during treatment are well known phenomena, but a PR presenting as a new pulmonary lesion after completion of treatment is extremely rare, and little is known about the management of such cases. A 44-year-old man was diagnosed with pulmonary TB. His sputum cultures became negative 45 days after the initiation of standard anti-TB treatment. Upon the patient's completion of 6 months of anti-TB therapy, computed tomography revealed a new irregularly shaped mass in the lower left pulmonary lobe. A transbronchial lung biopsy (TBLB) revealed caseous necrosis and granulomatosis surrounded by epithelioid and multinucleated giant cells. Cultures of both the TBLB specimen and bronchoalveolar lavage fluid remained negative for TB. The CT shadow disappeared 6 months later without further administration of anti-TB drugs. Careful observation without therapy may be sufficient for a patient treated for TB who develops a PR upon completion of treatment, if the patient has achieved a bacteriological remission., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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.

To define the immunopathologic mechanism underlying pulmonary Mycobacterium avium-intracellulare complex (MAC) disease in patients without AIDS, the ability of CD4(+) and gammadelta T cells to induce growth inhibition of MAC in monocytes was compared between patients and healthy control subjects. T cell-dependent growth inhibition and production of interferon-gamma and macrophage colony-stimulating factor decreased in patients. CD4(+) T and gammadelta T cells from patients were equally defective in inducing anti-MAC activity. The combination of these cytokines restored the ability of patients' T cells to control MAC growth. In experiments with allogeneic cocultures of gammadelta T cells and infected monocytes from patients and control subjects, healthy control T cells could augment growth inhibition of MAC in monocytes from patients, whereas patients' T cells could not, even in the presence of healthy control monocytes. These results indicate that the defect in T cells may be associated with impaired protective immunity against MAC in these patients.

We examined physical and blood statuses of 24 patients with pulmonary M. avium complex disease who entered our hospital from April 1993 to March 1997. Ten patients (41.7%) were diagnosed as primary infection type and 14 patients (58.3%) as secondary infection type. Twenty-four patients were classified to the following two groups: Group A was 14 patients who converted to MAC negative within six months after the admission and group B was 10 patients who continued to excrete MAC for more than six months after the admission. We made a comparison between group A and group B as to the results of physical and blood examinations on admission. Mean value of %IBW in group B was significantly lower (group B:74.4 +/- 8.9%, group A:82.9 +/- 12.7%, p < 0.05) than that of group A. The level of serum albumin in group B was significantly lower (group B: 3.39 +/- 0.53 g/dl, group A: 3.99 +/- 0.45 g/dl, p < 0.01) than that of group A. ChE in group B was significantly lower (group B: 321.2 +/- 94.5 IU/l, group A: 442.9 +/- 148.4 IU/l, p < 0.05) than that of group A. Group B was nutritionally depleted than group A. In conclusion, these findings suggested that nutritional support should be taken into consideration in combination with conventional chemotherapy in treating chronic, intractable MAC disease.

We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.

Diabetics are prone to bacterial infection in part, due to polymorphonuclear neutrophil dysfunction, but the precise mechanism is not yet fully explained. Of many complications, diabetes mellitus (DM) is one of the most common diseases, which causes pulmonary tuberculosis. To elucidate the mechanism of susceptibility to tuberculosis infection in patients with diabetes mellitus, we measured IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and autologous monocytes stimulated with live BCG in patients with pulmonary tuberculosis complicated with DM (TB + DM) or without DM (TB) and healthy controls. The levels of IFN-gamma and IL-12 production in TB patients were significantly lower than those in the control. These cytokine productions were also lower in TB + DM patients than in TB patients significantly. The level of IL-10 production in TB patients were highest among these three groups. The production of this cytokine in TB + DM patients was lowest. The level of IFN-gamma production was significantly lower in TB + DM patients under poor DM control than in those patients under good DM control and showed a significant negative correlation to HbA1c, an indicator of diabetic control. The period for negative conversion of culture finding in TB + DM patients under poor control was prolonged when compared with those in TB patients. These results demonstrated the difference in cytokines secretion profile between TB patients and TB + DM patients, and suggest that the immunological mechanism underlying pathogenesis of tuberculosis might work differently between these two patients groups.

Interferon-gamma (IFN-gamma) and interleukin-10 (IL-10)-producing ability of peripheral blood plastic-dish adherent cells and non-adherent cells obtained from patients with active pulmonary tuberculosis (N = 17) and healthy controls (N = 14) upon stimulation with purified protein derivatives (PPD) were assessed. Adherent cells and non-adherent cells were obtained two times from each patient with active pulmonary tuberculosis without any underlying diseases, on admission before the initiation of administering anti-tuberculous drugs and 2 months later from the negative conversion of Mycobacterium tuberculosis in sputum culture. ELISA was performed to measure IFN-gamma and IL-10 levels in culture media of adherent cells and non-adherent cells stimulated with PPD. IFN-gamma levels produced by non-adherent cells on admission were significantly higher than that of healthy controls (p < 0.001). Elevated IFN-gamma levels on admission was reduced after treatment for tuberculosis (p < 0.03), but still remained higher than that in healthy controls. IL-10 levels of non-adherent cells of patients were lower than those of healthy controls, although the difference was not significant. IL-10 levels produced by non-adherent cells on admission correlated with the time needed for negative conversion of bacilli in sputum culture (p < 0.05). IL-10 level produced by adherent cells from nutritionally normal patients were significantly higher than that of healthy controls (p < 0.05), and elevated IL-10 level was significantly reduced after therapy (p < 0.05). In the normonourished patients, the time needed for negative conversion of the bacilli in sputum culture of patients kept higher level of IL-10 of non-adherent cells (N = 5) was significantly longer than that of patients reduced IL-10 level after therapy. These results suggest that IL-10 produced by monocytes may diminish the TH1 responses of patients with pulmonary tuberculosis.

Although natural killer (NK) cells, which lyse certain tumors in vitro, have been shown to provide early defense mechanism against cancer growth and viral infection, possible role in the host defense against pulmonary tuberculosis remains undefined. A series of my studies have recently provided several evidence supporting the involvement of NK cells in the immunopathology of pulmonary tuberculosis. NK cell activity in patients with active pulmonary tuberculosis was significantly augmented compared with that in age-, sex- matched healthy controls, which suggests NK cells are activated in vivo in pulmonary tuberculosis. Lung NK cells from BCG-infected mice also are shown to be activated. Asialo GM 1 was demonstrated to be a novel surface marker of mice NK cells, which inhibited activation of NK cells by interferon. Chronic intractable tuberculosis was classified with a combination of NK cell activity and delayed-type hypersensitivity reaction to 2, 4-dinitrochrolbenzene. Subgroup defined with high NK cell activity and normal delayed-type hypersensitivity was characterized with moderate radiographical lesions and stable clinical course, suggesting the immune-spectrum classification was associated with clinical manifestations. Malnutrition has been suggested to be a risk factor associated with the development and reactivation of pulmonary tuberculosis. NK cell activity was significantly correlated with visceral proteins. IL-2 producing capability was significantly decreased in patients with serum albumin less than 3.5 g/dl. More recently, I established an in vitro system evaluating quantitative capability for intracellular killing by human monocytes, in which monocyte phagocytize Mycobacterium tuberculosis and subsequently inhibit intracellular replication of the organisms by adding some cytokines or cells. Purified NK cells by using discontinuous gradient centrifugation and magnetic separation technique were added to M. tuberculosis-infected monocytes monolayer. Purified NK cells inhibit intracellular replication within monocytes in dose response manner.

It is assumed that soluble tumor necrosis factor receptor I and II (sTNF-RI, II) play important roles in the regulation of tumor necrosis factor alpha (TNF-alpha) activity. We measured the levels of circulating sTNF-R in patients with active pulmonary tuberculosis (n = 31) and the correlation between TNF-alpha and sTNF-R in serum level was investigated. We also compared sTNF-R levels before and after the treatment in 7 cases. Significant increase of circulating sTNF-R were found in patients with tuberculosis compared with the normal controls (n = 28) (p < 0.01). Moreover, significant positive correlations were found between TNF-alpha and sTNF-R I and II (r = 0.520, r = 0.553) in serum comparing sTNF-R levels before and after the treatment for patients with tuberculosis, significant fall was found in sTNF-R I, but not in sTNF-R II. As a result, it is suggested that sTNF-R regulates TNF-alpha activity in patients with tuberculosis, and that sTNF-R I levels could be used as one of the indices to evaluate the clinical activity of tuberculosis.

Nutritional assessment was conducted in 30 patients with chronic, intractable pulmonary tuberculosis. More prevalent and severer protein-energy malnutrition was found in the chronic patients compared with that in newly-diagnosed, drug-sensitive tuberculous bacilli-excreting patients. Duration of excreting bacilli in 163 newly-diagnosed patients was found to be significantly associated with ChE, hypersensitivity reaction to PPD, lymphocytes transformation response to ConA before treatment. The grade of malnutrition was significantly associated with the reduction in delayed-type hypersensitivity response, ratio of CD4/CD8, IL-2 production by peripheral blood mononuclear cells and NK cell activity. Nutritional and immunological spectrum, which was classified with the combination of serum albumin level, hypersensitivity response to DNCB and NK cell activity, was significantly associated with clinical course and manifestations in patients with chronic, intractable pulmonary tuberculosis. TNF-alpha production by peripheral blood monocytes was significantly higher in moderately to mildly-malnourished tuberculous patients than that in healthy controls. TNF-alpha production in patients with severely-malnourished patients was significantly lower than that in healthy controls. Level in TNF-alpha production was inversely related with visceral proteins and the ratio of plasma amino acid BCAA/AAA. In conclusion these findings suggested that nutritional support should be taken in consideration in combination with conventional chemotherapy in treating chronic, intractable pulmonary tuberculosis.

Mucociliary transport (MCT) was studied in 22 patients with atypical mycobacteriosis (Group I : 16 with M. avium-intracellulare complex (MAC), Group II : 6 with M. kansasii) by aerosol inhalation cine-scintigraphy. In most of the patients, the MCT was abnormally slow both in the main bronchus and in the trachea, while in healthy controls the transport of the inhaled aerosol in the bronchus and the trachea were rapid and smooth. In both groups, the tracheal MCT was impaired in two thirds of the patients, while the MCT in the main bronchus was impaired in all except one in Group I and in two-thirds in Group II. The results indicate that the grade of bronchial impairment was higher in MAC than in M. kansasii infections. In atypical mycobacteriosis, especially in MAC infections, such impairment of MCT could be closely related to the disruption of local defence mechanisms in the airways.

We investigated the serum level of IL-8 and TNF-alpha using ELISA in 16 patients with active pulmonary tuberculosis before administration of antituberculous drugs and in age-, smoking habit-matched 20 healthy controls. The mean level of serum IL-8 in patients with active pulmonary tuberculosis was significantly higher than that in healthy controls (P < 0.001). The mean level of serum TNF-alpha in tuberculosis patients was also high, while TNF-alpha was not detectable in the sera of healthy controls. We also examined the relationship between clinical pictures mainly defined by radiographic findings and the serum levels of IL-8 and TNF-alpha. The serum IL-8 level of 9 patients with tuberculous cavity is significantly higher than that of 7 patients without cavity. (P < 0.05) We classified the patients with cavities into two subgroups according to the radiographic classification of the Japanese Society of Tuberculosis. Four patients with advanced lesions on chest X-ray showed higher serum IL-8 level than 5 patients with moderate lesions (P < 0.05). On the other hand, there was no correlation between serum TNF-alpha level and radiographic findings. These results suggest that IL-8 appears to be involved in the formation of tuberculous cavitary lesion.

The production of tumor necrosis factor alpha (TNF alpha) and of interleukin-6 (IL-6) by peripheral blood monocytes (PBMs) from patients infected with Mycobacterium avium intracellular complex (MAC) were assessed. Spontaneous release of both TNF alpha and IL-6 were greater during the active stage than during the inactive stage and in healthy controls. When the cells were stimulated with MAC-derived purified protein derivative B (PPD-B). TNF alpha production by PBMs in the active stage increased and IL-6 production by cells in both the active and inactive stages decreased. Moreover, the in vitro increase in TNF alpha production after stimulation in the active stage seemed to be related to the persistent MAC infection, which resulted in an exhaustion of nutrition. These results suggest that the ability of PBMs to produce TNF alpha and IL-6 in vitro is closely related to the clinical stage of MAC infection.

A survey on the nutritional status and cell-mediated immune function of 47 hospitalized patients with active pulmonary tuberculosis and healthy controls was conducted. In the patients group: 1) Anthropometric measurements, such as %ideal body weight (%IBW), %arm circumference (%AC), %arm muscle circumference (%AMC) and %triceps skin fold (%TSF), were significantly reduced. 2) Visceral proteins including serum albumin (Alb), transferrin (Tf), prealbumin (PA) and retinol binding protein (RBP) were significantly reduced. 3) The imbalance of plasma amino acids, which was characterized by the depression of Fischer ratio, a molar ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA), was observed. Fischer ratio was significantly correlated with anthropometric measurements (%IBW, %AC and %AMC). Delayed-type hypersensitivity to DNCB (2,4-dinitrochlorobenzene) and lymphocyte transformation to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly impaired in the patients group, whereas NK cell activity was higher than that of controls. Alb, PA, RBP and Fischer ratio were significantly lower in the patients with reduced DNCB reaction than in those with normal responses. Lymphocyte transformation was significantly correlated with Fischer ratio, and NK cell activity was significantly correlated with Alb, PA, RBP. These data may suggest that the imbalance of plasma amino acids represented by the reduction of Fischer ratio and the depletion of visceral proteins are closely related to the impairment of lymphocyte function in the patients with active pulmonary tuberculosis.

A study was made on a patient with anorexia nervosa complicated with pulmonary tuberculosis treated with intravenous hyperalimentation (IVH). A 24-year-old female was admitted to our hospital because of progressive loss of body weight during medication for pulmonary tuberculosis at another hospital. She was diagnosed as having anorexia nervosa. After the nutritional assessment IVH was performed. As a result of IVH, her body weight increased and her nutritional deprivation, (i.e., low visceral proteins, low branched amino acids, etc.) recovered. Nutritional support was effective upon treating pulmonary tuberculosis.

An autopsy case of 63-year old male of atypical mycobacteriosis with severe scoliosis was reported. He was diagnosed as atypical mycobacteriosis in 1981 and controlled by antimycobacterial treatment. But since 1989, dyspnea and sputum have been increasing, new abnormal shadow in company with progression of curvature of the scoliosis was revealed on the chest roentgenogram. In spite of various treatments for mycobacteriosis, he died of respiratory failure. The aggravation of this mycobacteriosis brought on advancement of malnutrition and impairment of cell mediated immunity. Findings of autopsy showed the remarkable chest wall deformity and tuberculous change of the lung parenchyma. In this case, chest deformity was thought as the major risk factor of onset of mycobacterial mycobacteriosis.

A clinical investigation was carried out in 39 patients with atypical mycobacteriosis (AM). The patients at our hospital diagnosed as having AM during an 11-year period from 1981 to 1991 were reviewed in this study. The incidence of AM among all of mycobacterial infections has been increasing since 1988. The atypical mycobacteria detected included M. avium complex (MAC) in 79%, M. kansasii in 26%, and other organisms in 5%. Patients who had primary infection without underlying respiratory disease were compared with those who had secondary infection. In secondary infection, MAC was detected in the sputum of a high percentage of patients and was positive for more than 6 months despite therapy. Gamma globulin levels were also increased in patients with secondary infection. Cell mediated immunity was examined by the DNCB reaction and the detection of CD4- and CD8- positive T lymphocytes. The DNCB skin reaction was positive in 6 out of 26 patients with secondary infection. The percentage of CD8- positive T lymphocytes was higher in patients with secondary disease. Fischer's ratio (indicating the balance of plasma amino acids) was also examined as an index of the nutritional status. It was significantly lower in secondary infection compared with primary infection. Moreover, secondary infection was associated with a lower positive rate for the DNCB skin reaction and a lower Fischer's ratio when compared with pulmonary tuberculosis. Thus impairment of cell-mediated immunity, malnutrition, and a poor prognosis were significantly more common in secondary infection compared with primary infection.

Three young adults advanced pulmonary tuberculosis due to delay of therapy were reported. In case 1 and 3, their delays resulted from difficulty in diagnosis, in case 2, from neglecting medical counseling. Each cases revealed bilateral diffuse shadows on chest roentgenograms on admission, which were typical shadows of advanced pulmonary tuberculosis. Malnutrition might contribute to the development of the diseases, which were improved by anti-tuberculosis therapy and hyperalimentation therapy. These cases were suggested some clinical problems characteristic of pulmonary tuberculosis of young adults.

Patients with diabetes mellitus (DM) show an increased susceptibility to bacterial infections due to the presence of neutrophil dysfunction. Susceptibility to tuberculosis has also been reported in such patients, however, the reason remains unclear. This study measured the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) by the peripheral monocytes of patients diagnosed with pulmonary tuberculosis accompanied by DM (TB+DM) and patients without DM complications (TB) using age-matched, healthy control subjects for comparison. Also examined was the relationship between cytokine production and DM control. The results were as follows: (1) The production of IL-1 beta, TNF alpha and IL-6 in TB patients was significantly higher than that observed in the healthy control subjects. (2) The production of IL-1 beta, TNF alpha and IL-6 in TB+DM patients was significantly lower than that observed in the TB patients. (3) The production of IL-1 beta and TNF alpha in TB+DM patients with poor control was significantly lower than that observed in the patients with good control. (4) The TNF alpha production had a significant inverse correlation to HbA1c in the TB+DM patients. This study demonstrated that the production of cytokines is impaired in TB+DM patients and suggests a close correlation between tuberculosis immunity and DM.

We reported a case who had suffered from severe pulmonary tuberculosis in association with severe malnutrition. A 19-year-old man was admitted complaining of high fever, productive cough and body weight loss. Before admission, he worked as a cook for long hours a day and had meals irregularly. On admission, he was cachexic. Coarse crackles were auscultated on the both lung field, and the liver was enlarged. Chest X-ray revealed multiple ringed and mottled shadows mainly in bilateral upper and middle lung field. Laboratory examination revealed inflammatory reaction defined by an increase of white blood cells, accelerated erythrocyte sedimentation rate and positive CRP, impairment of liver function and cell-mediated immunity, hypoxemia and restrictive lung dysfunction. Ziehl-Neelsen stain of sputum showed a large number of acid fast bacilli. The assessment of his nutritional status showed decrease in anthropometric measurements, visceral proteins and the Fischer ratio, which suggested that he was in the status of protein-calorie malnutrition in association with amino acid imbalance. He was treated with nutritional therapy in addition to antituberculous drugs, which improved his clinical symptoms, laboratory data and nutritional assessment. These results suggested the importance of nutritional assessment and nutritional therapy based on it.

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)

Natural killer (NK) cell activity, which may provide defence mechanism in the immune surveillance system, was studied in 38 patients with active pulmonary tuberculosis and 54 sex-, and age-matched healthy controls. The mean NK cell activity in patients with active pulmonary tuberculosis (58.7 +/- 26.4%) was significantly higher (P less than 0.001) than that in healthy controls (17.4 +/- 12.2%). Classifying the patients into three groups according to the state of excretion of tubercle bacilli, the mean NK cell activity in newly diagnosed patients was 43.2 +/- 20.7%, in advanced disease 59.4 +/- 30.3%, and in successfully treated patients 71.9 +/- 25.9%.

We examined natural killer (NK) cell activity and delayed-type hypersensitivity reaction to 2,4-dinitrochlorbenzene (DNCB) in the spectrum of chronic, intractable pulmonary tuberculosis. A high reactive group as defined by high NK cell activity and positive reaction to DNCB were characterised by stable clinical courses assessed by radiographical and clinical changes. A low reactive group defined by non-augmented NK cell activity and negative reaction to DNCB were characterised by progressive clinical courses. Although far advanced radiographic lesions were observed more frequently in the low reactive group and moderately advanced lesions more frequently in the high reactive group, there was not a significant statistical trend.

Although epidemiological studies have shown that malnutrition is associated with the reactivation and development of pulmonary tuberculosis, little is known about their nutritional status. We studied comprehensive profile of their nutritional status. We also studied the effects of malnutrition on cell-mediated immunity in tuberculosis patients. Nutritional status was assessed by anthropometric measurements and biochemical examinations, and cell-mediated immunity was evaluated by delayed-type hypersensitivity (DTH) reaction, lymphocyte transformation and natural killer (NK) activity in 47 patients with active pulmonary tuberculosis and 47 healthy controls. Cytokine production including IL-2, IL-1 was also examined. Anthropometrics and visceral proteins were significantly lower in tuberculosis patients. Fischer ratio (BCAA/AAA), an index of plasma amino acids imbalance, was significantly (p less than 0.01) lower in the patients. DTH to 2, 4-dinitrochlorobenzene and lymphocytes transformation were attenuated in the patients. NK activity was reduced in patients with severe pulmonary tuberculosis. The patient subgroup with reduced DTH was more malnourished than another one with normal DTH. The Fischer ratio correlated significantly with lymphocyte transformation response and visceral proteins and BCAA correlated with NK activity. IL-2 production was remarkably reduced in the patient subgroup whose serum albumin was less than 3.5 g/dl. IL-1 production was remarkably reduced in the patient subgroup whose serum albumin was less than 2.5 g/dl. Patient subgroup whose serum albumin level was more than 2.5 g/dl and less than 3.5 g/dl, produced remarkably more IL-1 than those whose serum albumin was more than 3.5 g/dl. These results suggested that malnutrition characterized by the reduction of the Fischer ratio was associated with impairment of cell-mediated immunity and cytokine production in pulmonary tuberculosis.