Serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in large cohorts of healthy adults.

Enzyme linked immunosorbent assays were used to measure serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in 681 healthy adults (range 18 yr-101 yr). Immunoreactive thymosin alpha 1 was found to occur at a geometric mean of 540 pg/ml with a range from 252 to 1158 pg/ml. There were no differences in the levels when analyzed according to race, sex or age. Immunoreactive thymosin beta 4 was measured at a geometric mean of 12.6 ng/ml with a range from 6.9 to 23.0 ng/ml. There were no differences in the levels when analyzed according to race or sex, however, there was a slight upward trend with increasing age. This data may be useful as a reference when monitoring clinical studies, determining the kinetics of drug metabolism and distinguishing patient groups with elevated levels of either of these peptides.     

Cytokines in symptomatic asthma airways.

To determine whether cytokines are generated in vivo in subjects with asthma, we have measured cytokine levels (tumor necrosis factor [TNF], granulocyte-macrophage-colony-stimulating factor [GM-CSF], interleukin [IL]-1 alpha, IL-1 beta, IL-2, IL-4, and IL-6) in the airways of subjects with symptomatic (N = 24) and asymptomatic (N = 9) asthma with immunoassays (GM-CSF, IL-1 alpha, IL-1 beta, IL-2, and IL-4) or bioassays (TNF and IL-6) and the polymerase chain reaction (IL-1 beta and TNF). Significant levels of TNF (578 +/- 917 pg/ml versus 24 +/- 29 pg/ml) (p = 0.01), GM-CSF (24 +/- 41 pg/ml versus less than 8 pg/ml) (p = 0.02), and IL-6 (225 +/- 327 pg/ml versus 7 +/- 12 pg/ml) (p = 0.01), but not IL-1 alpha or IL-4, were detected in the bronchoalveolar lavage fluid (BALF) of patients with symptomatic compared with BALF of patients with asymptomatic asthma. Levels of IL-1 beta (266 +/- 270 pg/ml versus less than 20 pg/ml) (p = 0.001) and IL-2 (1.4 +/- 2.8 ng/ml versus less than 0.3 ng/ml) (p = 0.05) in BALF in patients with symptomatic compared with that in BALF levels in patients with asymptomatic asthma suggested activation of alveolar macrophages and T cells. Thus, in episodes of asthma, several cytokines, including TNF, GM-CSF, IL-1 beta, IL-2, and IL-6 are detectable in BALF.     

Improved ELISA to measure thymosin alpha 1: comparison of whole and absorbed antisera

An improved microELISA to measure thymosin alpha 1 (T alpha 1) is described which uses a rabbit antibody against T alpha 1 that has been absorbed with a synthetic C-14 fragment of T alpha 1. This assay is compared to the previous assay which used the whole antisera. The antibodies to T alpha 1 are preincubated with the standard or human sera overnight at 4 degrees C, then incubated for an additional 24 h in microtiter plates coated with T alpha 1. Using the whole antiserum, the average T alpha 1 level was 2480 +/- 1110 (mean +/- S.D.) pg/ml by ELISA and 2360 +/- 870 pg/ml by radioimmunoassay (RIA) in eight different samples of human cord sera. Using the N-specific absorbed antiserum the mean T alpha 1 level was 11,800 +/- 4800 pg/ml by ELISA and 10,600 +/- 5200 pg/ml by RIA. Recoveries of exogenously added T alpha 1 are complete (109 +/- 25% for whole and 108 +/- 15% for absorbed antisera). The absorbed antiserum has an increased affinity for the amino acid terminal region of T alpha 1 and the T alpha 1 values by use of absorbed antisera are significantly higher (3-5 x) than those measured using the whole antisera. Thus, the absorbed antisera produces an ELISA which is more sensitive and specific for serum thymosin alpha 1.     

Serum cytokine responses during acute human granulocytic ehrlichiosis

Human granulocytic ehrlichiosis (HGE) is caused by obligate intracellular bacteria in the Ehrlichia phagocytophila group. The disease ranges from subclinical to fatal. We speculated that cell-mediated immunity would be important for recovery from and potentially in the clinical manifestations of HGE; thus, serum tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), gamma interferon (IFN-gamma), IL-10, and IL-4 concentrations were studied. IFN-gamma (1,035 +/- 235 pg/ml [mean +/- standard error of the mean]) and IL-10 (118 +/- 46 pg/ml) concentrations were elevated in acute-phase sera versus convalescent sera and normal subjects (P 相似文献   

Immunological markers of disease progression in patients infected with the human immunodeficiency virus.

Identification of inexpensive and technically simple immunological tests useful in predicting the progression to AIDS in human immunodeficiency virus (HIV)-infected patients would be especially welcome in developing countries, in which 80% of HIV-infected patients reside and health budgets are low. In the current study, we evaluated CD4+ and total lymphocyte counts and the concentrations in serum of beta 2-microglobulin, p24 antigen, and immunoglobulin A (IgA) as predictors of disease progression in 74 Panamanian HIV-positive patients and 50 HIV-negative healthy individuals. Total lymphocyte and CD4(+)-cell counts for AIDS patients (1,451 +/- 811 cells/microliters, P < 0.001, and 238 +/- 392 cells/microliters, P < 0.0001, respectively and asymptomatic patients (2,393 +/- 664 cells/microliters, P > 0.05, and 784 +/- 475 cells/microliters, P < 0.001, respectively) were lower than those observed for healthy subjects (2,596 +/- 631 cells/microliters and 1,120 +/- 296 cells/microliters, respectively). The levels of beta 2-microglobulin and IgA in serum were significantly elevated in patients with AIDS (5.7 +/- 3.6mg/liter, P < 0.001, and 541 +/- 265 mg/dl, P < 0.0002, respectively) and asymptomatic infected subjects (3.4 +/- 2.1 mg/liter, P = 0.001, and 436 +/- 216 mg/dl, P < 0.0001, respectively) compared with the levels in healthy subjects (2.2 +/- 0.7 mg/liter and 204 +/- 113 mg/dl, respectively). Nonstatistically significant differences (P > 0.05) for concentrations of p24 antigen between asymptomatic infected patients (29 +/- 13 pg/ml) and AIDS patients (40 +/- 23 pg/ml) were observed. Total lymphocyte counts of 1,750 cells/microliters or less, CD4 counts of 200 cells/microliters or less, beta 2-microglobulin concentrations in serum of 4 mg/liter or higher, concentrations of IgA in serum of 450 mg/dl or higher, and the presence in serum of p24 antigen were correlated with elevated risks for developing AIDS. Monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring the immune status of HIV-positive patients.     

Normalization of serum prolactin levels in hemodialysis patients on recombinant human erythropoietin

Correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) has been reported to improve sexual function. As elevated serum prolactin levels are believed to contribute to altered sexual function in uremia, we followed serum prolactin and testosterone levels during four months of r-HuEPO therapy. Within these four months, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly, from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were in the lower normal range in male patients and remained unchanged during r-HuEPO therapy. Sexual function improved in four out of seven males, and five out of nine female patients started to have regular menstruations again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO may improve sexual function by lowering elevated serum prolactin concentrations.     

No difference in serum leptin concentrations between urban-dwelling Austronesians and Non-Austronesians in Papua New Guinea.

Pacific Islands populations can be broadly divided into Austronesians (AN) and Non-Austronesians (NAN); obesity and type 2 diabetes are prevalent in the former, although leptin levels in both groups have seldom been investigated. Thirty-seven (20 male and 17 female) adult pairs, matched by age and percent body fat, from AN-speaking Balopa and NAN-speaking Huli, all of whom migrated to settle in Port Moresby, the capital of Papua New Guinea, were selected for comparison of their serum leptin concentrations. The Balopa did not differ significantly from the Huli in age (30.5 +/- 9.7 and 30.0 +/- 8.7 years for males, 33.7 +/- 8.9 and 34.1 +/- 7.5 years for females, respectively) or percent body fat (19.4 +/- 5.6 and 18.8 +/- 4.6 for males, 34.1 +/- 6.2 and 33.3 +/- 5.0 for females), although the BMI of females was lower in the Balopa (26.4 +/- 4.9) than in the Huli (29.7 +/- 4.7) (P = 0.02). In both ethnic groups, females had markedly higher leptin concentrations than males, but there was no significant inter-group difference in males (3.5 +/- 2.6 and 3.1 +/- 4.7 ng/ml, P = 0.14) or females (22.7 +/- 12.9 and 19.7 +/- 11.9 ng/ml, P = 0.40), after controlling for lifestyle factors and serum lipids. Multiple regression analysis revealed that significant predictors of leptin concentration were % body fat (beta = 0.58), sex (male, 0; female, 1; beta = 0.27), and smoker status (non-smoker, 0; smoker, 1; beta = -0.15) (R(2) = 0.80), implying that the leptin concentration was primarily determined by lifestyle-derived body fatness. In conclusion, the NAN populations do not endogenously differ in leptin status from the AN populations, who have been recognized as a typical group with a "thrifty" genotype.     

Elevated beta 2-microglobulin and lysozyme levels in patients with acquired immune deficiency syndrome

beta 2-Microglobulin (beta 2-M) levels in sera and urines, and lysozyme levels in sera, were quantitated in healthy heterosexual men and several groups of homosexual males. The mean beta 2-M levels in sera and urines and lysozyme levels in sera of healthy heterosexual and homosexual men were not significantly different. However, beta 2-M levels in patients with lymphadenopathy syndrome and AIDS were elevated. The mean beta 2-M level in sera of 11 patients with the lymphadenopathy syndrome was 4016 +/- 473 micrograms/l (SEM) (P less than 0.001) and 5409 +/- 462 micrograms/l (P less than 0.001) in 27 patients with AIDS. Similarly, beta 2-M levels in the urines of patients with chronic diarrheal syndrome, lymphadenopathy syndrome, and those meeting the CDC surveillance definition of AIDS were also significantly elevated (P less than 0.025). The mean lysozyme levels in the sera of 11 patients with the lymphadenopathy syndrome was 16.58 +/- 0.04 microgram/ml, and in 27 patients with AIDS 15.40 +/- 1.16 microgram/ml, compared to the mean level obtained in normal heterosexual men of 6.67 +/- 0.42 microgram/ml (P less than 0.001). The results of this study suggest that measuring beta 2-M in serum and urine and lysozyme levels in serum might provide additional useful parameters for the evaluation of patients with AIDS and prodromal syndromes.     

Micro ELISA for measurement of parathymosin alpha utilizing a monoclonal antibody

A monoclonal antibody to the non-thymosin alpha 1 overlapping sequence of parathymosin alpha was used to develop a micro ELISA to measure parathymosin alpha. Parathymosin alpha levels were measurable in both mouse tissue extracts and in human adult and cord serum. To measure parathymosin alpha, a 40% ammonium sulfate precipitated monoclonal antibody specific for the parathymosin alpha fragment was preincubated with the parathymosin alpha fragment or samples for 4 hours at 4 degrees C, incubated an additional 24 hours in microtiter plates coated with the parathymosin alpha fragment and then assayed by the biotin-avidin-alkaline phosphatase method. Using the assay, parathymosin alpha could be measured over a range of 5 to 630 ng/ml and cross-reactivity with thymosin alpha 1 was not observed. The parathymosin alpha level was 400 +/- 140 (mean +/- SD) ng/ml in normal human sera (n = 12) and 150 +/- 80 ng/ml in cord sera (n = 12). The concentration of parathymosin alpha was highest in tissue extracts of mouse liver (153 +/- 40 micrograms parathymosin alpha per g of tissue), kidney (125 +/- 33), and lung (105 +/- 38). Levels were lowest in thymus (81 +/- 20), spleen (83 +/- 23), and brain (71 +/- 23).     

Protein A of Staphylococcus aureus evokes Th1 type response in mice.

Protein A (PA) of Staphylococcus aureus is known to elicit several cytokines such as IFN gamma, TNF alpha and IL1. However, it has not been delineated yet as to which differentiation pathway lymphocytes follow after stimulation by PA. In this report, we attempted to collect such evidences. Cytokines, such as IFN gamma, IL2, IL4, IL6, IL10, TNF alpha, IL1alpha and IL1beta were measured in serum by ELISA. Our results show that 1 microg dose of PA stimulates the production of IFN gamma (115 +/- 5 pg/ml), TNF alpha (250 +/- 8 pg/ml) and IL1alpha (100 +/- 5 pg/ml) as compared to control levels of, 22 +/- 2, 20 +/- 2 and 35 +/- 3 pg/ml respectively whereas IL2 and IL1beta secretion were less (beyond the lower detection limit of the kit and 25 +/- 1 pg/ml, respectively) as compared to control (28 +/- 2 and 52 +/- 4 pg/ml, respectively). Larger dose of PA (10 microg) increases the expression of IL2 (75 +/- 3 pg/ml), TNF alpha (1380 +/- 120 pg/ml), IL1alpha (495 +/- 10 pg/ml) and IL1beta (110 +/- 7 pg/ml) as compared to controls described above. We also observed that 1 microg dose of PA decreases IL4, IL6 and IL10 secretion to 9 +/- 1, 10 +/- 1 and 10 +/- 2 pg/ml, respectively, whereas 10 microg dose also decreased them to 11 +/- 1, 12 +/- 2 and 30 +/- 4 pg/ml, respectively as compared to the background controls, i.e. 50 +/- 5, 50 +/- 2 and 215 +/- 9 pg/ml respectively. The ratio of IFN gamma to IL4 increased and the peak value at 4 h, came to 13 +/- 1 and 9.6 +/- 0.5 with 1 microg and 10 microg PA, respectively, which is an established parameter indicating a Th1 type response. Flow cytometry analysis of CD4+/CD8+ cells, and c-myc protein expression by splenocytes indicate that 1 microg dose of PA causes 2-fold increase of CD4+ cells with no change in CD8+ cells, and 10-fold increase in c-myc protein, whereas 10 microg dose increases CD4+ cells 4-fold, CD8+ cells 3-fold and c-myc protein 100-fold. The cell cycle data shows an induction of apoptosis in thymocytes and splenocytes with the large dose (10 microg), whereas the 1 microg dose does not show any apoptosis. This report indicates that a Th1 response is induced in mice, after PA inoculation at a dose of 1 microg animal. Thus, cytokine mediated therapeutic strategies should consider the fact that an induction of large concentration of some cytokines might become detrimental to the host.     

The effect of trimetazidine on C-reactive protein, cytokines and adhesion molecules in the course of acute myocardial infarction

The aim of this randomised, double-blind, placebo controlled, parallel group study was to assess the effect of trimetazidine (TMZ), a potent antiischaemic drug, on plasma C-reactive protein (C-RP), cytokine and adhesion molecule levels. The study population consists of 18 patients (16 males, 2 females, average age 56.45 +/- 10.97 years) with acute myocardial infarction admitted within 6 hours after onset of symptoms and treated with streptokinase. Blood samples were taken at 3-hour intervals during the time of treatment. All patients were randomised blindly using a centralised randomisation process, between trimetazidine (40 mg bolus i.v. then 60 mg per day for 48 hours intravenously in glucose infusion) or placebo group. Plasma C-RP level was significantly lower in TMZ group (39.5 mg/ml +/- 9.7 mg/ml) as compared to placebo (75.7 +/- 29.4 mg/ml, p < or = 0.001) and peaked 28 hours later in TMZ group. Plasma interleukin 6 (IL 6) level showed a sharp peak 9 hours after the onset of the symptoms in TMZ group (116.9 +/- 180.2 pg/ml vs. 45.4 +/- 37.9 pg/ml) and was increased up to 30 hours after the onset of the symptoms. Plasma interleukin 1 beta (IL 1 beta) was also higher in TMZ group notably 21 hours after the onset of symptoms (26.4 +/- 9.3 pg/ml vs. 16.2 +/- 2.4 pg/ml). TMZ group showed lower plasma E-selectin levels. Plasma IL 8, TNF alpha and ICAM 1 levels were without statistical significant differences. The present study demonstrates a significant reduction of plasma C-reactive protein level in the course of acute myocardial infarction treated with streptokinase and intravenous trimetazidine infusion compared with the group of patients without trimetazidine treatment.     

A two-site monoclonal enzyme immunoassay for pregnancy-associated alpha 2-glycoprotein

A two-site monoclonal enzyme immunoassay (MEIA) was developed for the determination of pregnancy-associated alpha 2-glycoprotein (PA alpha 2G) in serum. The minimum detectable level was 35 ng/ml. No immunochemical interaction with the closely related alpha 2-macroglobulin was found. Serum levels in 145 normal healthy males and non-pregnant females were 1.8 +/- 2.8 micrograms/ml (mean +/- SD), respectively, both significantly lower than previously reported. The distribution in the normal population was characteristically different when males and females were compared. No increase with age was found. During pregnancy, a significant increase in serum concentration was observed with average levels of 320 +/- 200 micrograms/ml at term (mean +/- SD), a 50-fold increase in concentration. As a tumor marker for breast and ovarian cancer, PA alpha 2G was found to be of no value. The present study emphasizes that a reevaluation of PA alpha 2G levels must be undertaken in order to assess the clinical and biological significance of this protein.     

CXCR3 and CCR5 ligands in rheumatoid arthritis synovium

The pathogenesis of rheumatoid arthritis (RA) may be mediated by Th1-type T cells. Since chemokine receptors CXCR3 and CCR5 are preferentially expressed on Th1 cells, we tested the expression and regulation of several chemokines, including those that signal through CXCR3 (interferon-gamma-inducible protein of 10 kDa, IP-10, CXCL10; and monokine induced by interferon-gamma, Mig, CXCL9) and CCR5 (macrophage inflammatory protein (Mip)-1 alpha, CCL3; and Mip-1 beta, CCL4) in RA synovial fluids, synovial tissues, and blood. Synovial fluid (SF) protein levels of IP-10 (32.1 +/- 10.5 ng/ml), Mig (15.0 +/- 6.4 ng/ml), Mip-1 beta (0.7 +/- 0.3 ng/ml), and Mip-1 alpha (0.8 +/- 0.1 ng/ml) were 100-, 50-, 25-, and 2-fold elevated in RASF compared to control SF (P < 0.001, P < 0.001, P < 0. 001, and P < 0.02, respectively). Tissue levels of IP-10, Mig, and Mip-1 beta were significantly higher in RA than in OA (P < 0.01). Serum levels of IP-10 (3.1 +/- 1.2 ng/ml) were higher in patients with seropositive RA compared to controls (1.2 +/- 0.2 ng/ml) (P < 0.02). There was a gradient of IP-10, Mig, Mip-1 alpha, and Mip-1 beta from the blood into the synovial fluid in RA. Infiltrating T cells around high endothelial venules in RA synovium and 90 +/- 3% of SF CD3(+)CD4(+) T cells expressed CXCR3, and 85 +/- 2% of SF CD3(+)CD4(+) T cells expressed CCR5. Chemokines, including IP-10, Mig, Mip-1 alpha, and Mip-1 beta, may participate in the selective recruitment of CCR5(+)CXCR3(+) T cells to the inflamed synovium.     

Evaluation of serum troponin T measurement in acute myocardial infarction]

A monoclonal solid phase enzyme immunoassay has been developed for the detection of human troponin T. The serum troponin T levels in healthy subjects gave 0.05 +/- 0.06 ng/ml in total (n = 176), 0.06 +/- 0.07 ng/ml in males (n = 79) and 0.03 +/- 0.05 ng/ml in females. Within-run and between-run precision (CVs) of the assay were less than 5%. Various common interferents tested did not affect on the assay, but higher titer of rheumatoid factor, and anti-coagulants such as EDTA, heparin oxalate and citrate affected the assay. In all patients with defined acute myocardial infarction, serum troponin T levels increased 7 to 10 folds the upper reference range within 6 hours after the onset of chest pains and maximum elevation of serum troponin T level was at around 20 hours and its levels remained elevated for 7 to 20 days. Specificity and sensitivity for acute myocardial infarction was 92.4% and 100%, respectively. The results indicated that troponin T measurement improved the diagnostic efficiency for the detection of myocardial necrosis as compared with conventionally used cardiac enzymes and was an effective tool for the confirmation of the reperfusion by PTCA and PTCR.     

Sex related differences in serum gastrin concentrations and G- and D-cell populations of the gastric mucosa in guinea-pigs (experimental RIA and immunocytochemical study).

In the present study antral G-cells which secrete gastrin and antral and fundic D-cells which secret somatostatin, an inhibitor of gastric acid secretion were revealed immunocytochemically and the population size estimated along with serum gastrin levels in ten male and eight female guinea pigs. Serum gastrin, antral G-cells, antral D-cells and fundic D-cells were 41.90 +/- 6.10 SD pg/ml, 210 +/- 18.03 SD cells/cm, 128.20 +/- 17.64 SD cells/cm and 121 +/- 17.91 SD cells/cm respectively in males and 35 +/- 4.62 SD pg/ml, 176 +/- 13.80 SD cells/cm, 108.40 +/- 6.90 SD cells/cm and 106.8 +/- 6.50 SD cells/cm respectively in females. The differences in serum gastrin levels, antral G-cell population and antral D-cell population between the two sexes were statistically significant (P less than 0.05, P less than 0.001, P less than 0.01). It is possible that endogenous androgens induce a relative hyperplasia and endogenous oestrogens a relative hypoplasia of G-cells. Antral D-cell differences may reflect an adaptive hormonal mechanism to the possible different states of gastric secretory functions.     

Sex related differences in serum gastrin concentrations and G- and D-cell populations of the gastric mucosa in guinea-pigs (experimental RIA and immunocytochemical study)

In the present study antral G-cells which secrete gastrin and antral and fundic D-cells which secret somatostatin, an inhibitor of gastric acid secretion were revealed immunocytochemically and the population size estimated along with serum gastrin levels in ten male and eight female guinea pigs. Serum gastrin, antral G-cells, antral D-cells and fundic D-cells were 41.90 +/- 6.10 SD pg/ml, 210 +/- 18.03 SD cells/cm, 128.20 +/- 17.64 SD cells/cm and 121 +/- 17.91 SD cells/cm respectively in males and 35 +/- 4.62 SD pg/ml, 176 +/- 13.80 SD cells/cm, 108.40 +/- 6.90 SD cells/cm and 106.8 +/- 6.50 SD cells/cm respectively in females. The differences in serum gastrin levels, antral G-cell population and antral D-cell population between the two sexes were statistically significant (P less than 0.05, P less than 0.001, P less than 0.01). It is possible that endogenous androgens induce a relative hyperplasia and endogenous oestrogens a relative hypoplasia of G-cells. Antral D-cell differences may reflect an adaptive hormonal mechanism to the possible different states of gastric secretory functions.     

Restrictive lung disease and serum TGF-beta1 in thalassemia major children

A cross sectional study was performed in 21 thalassemia major (TM) children at King Chulalongkorn Memorial Hospital during March to August, 2003 to determine whether restrictive lung disease (RLD) was related to serum transforming growth factor-beta 1 (TGF-beta1). All studied patients (57% female, age 11.2 +/- 2.6 yrs, duration of transfusion 7.7 +/- 4.1 yrs) never had desferoxamine treatment and their pulmonary function, serum ferritin and serum TGF-beta1 were evaluated. Five (24%) had RLD. RLD patients had significantly longer durations of transfusion and higher serum ferritin levels than non-RLD patients (9.1 +/- 1.9 vs 5.5 +/- 3.2 yrs; p = 0.03 and 3,816.6 +/- 1,715.9 vs 2,084.5 +/- 1,504.8 ng/ml; p = 0.04, respectively). TM children had lower serum TGF-beta1 levels than normal children (7.9 vs 78.8 pg/ml; p < 0.001). The serum TGF-beta1 level was not different between RLD and non-RLD patients (13.3 vs 4.2 pg/ml; ns), concluding that RLD was related to longer duration of transfusion and higher serum ferritin but not related to serum TGF-beta1 levels.     

Induction of phagocyte-stimulating cytokines by in vitro stimulation of human peripheral blood mononuclear cells with Haemophilus influenzae

The aim of this study was to analyse the in vitro response of human peripheral blood mononuclear cells to stimulation with killed Haemophilus influenzae strains of different capsular types, isolation sites and from cases with different forms of infections. The mean stimulatory index using 10(6) bacteria/well was 10, and 80 when 10(8) bacteria/well were used for stimulation. The mean+/-SD level was 13+/-4 ng/ml for interleukin (IL)-1beta, 128+/-73 ng/ml for IL-6, 203+/-122 ng/ml for IL-8, 3160+/-1220 pg/ml for IL-10, 29+/-40 pg/ml for IL-12, 2800+/-1790 pg/ml for tumour necrosis factor (TNF)-alpha and 4+/-7 ng/ml for interferon (IFN)-gamma, when stimulating cells with the lower dose of 10(6) bacteria/well. Using the higher bacterial dose, the levels of IL-1beta, TNF-alpha and IL-12 remained similar, whereas the IL-6, IL-8 and IL-10 levels were significantly lower, and IFN-gamma levels were significantly higher. Strains isolated from the bronchial tree induced significantly higher levels of IFN-gamma and significantly lower levels of IL-6, IL-8 and IL-10 than strains from other isolation sites. In conclusion, H. influenzae generated phagocyte-activating cytokines and an IL-10/IL-12 ratio that was 1090 times that described previously for Streptococcus pneumoniae.     

Defective in vitro gamma interferon production and elevated serum immunoreactive thymosin beta 4 levels in patients with inflammatory bowel disease

Gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells (PBM) was measured in 21 patients with Crohn's disease, in 15 patients with ulcerative colitis, in 12 patients with non-IBD gastrointestinal disease (disease control), and in 28 healthy controls. T-cell subset proportions and serum levels of thymosin alpha 1 and thymosin beta 4, two hormonelike thymic peptides, were also determined. No differences were seen in T-cell subset proportions in patients with Crohn's disease or ulcerative colitis when compared to healthy controls or to the disease-control group. In vitro IFN-gamma production was markedly decreased in Crohn's disease and in untreated, but not treated, patients with ulcerative colitis. Preincubation of PBM prior to the addition of inducer mitogen resulted in enhanced IFN-gamma production in patients with Crohn's disease or ulcerative colitis which significantly exceeded that seen either in healthy controls or in the disease-control group. Serum thymosin alpha 1 levels were comparable in all study groups; however, serum thymosin beta 4 concentrations were significantly higher in all patient groups than in the healthy controls. These results confirm a defective in vitro IFN-gamma production in patients with IBD which is apparently independent of endocrine thymus regulation.