The pro- and anti-inflammatory markers in patients with acute myocardial infarction and chronic stable angina

The aim of this study was to assess the plasma levels of VEGF and interleukin-10 in patients with acute myocardial infarction (AMI) and stable chronic angina (SA) and correlate the values with traditional CHD risk factors, left ventricular ejection fraction (LVEF) and established inflammatory marker hsCRP. Fifty patients with AMI and 30 with SA were enrolled. IL-10 levels in AMI patients were lower than in SA patients (9.81 +/- 5.0 versus 22.63 +/- 8.38 pg/ml, p < 0.00001). IL-10 levels were lower in AMI and SA patients with multiple CHD risk factors than in patients < or = 2 risk factors (SA: 19.48 +/- 2.94 versus 23.77 +/- 2.94 pg/ml; p < 0.005; AMI: 8.64 +/- 4.43 versus 11.85 +/- 4.09 pg/ml; p < 0.05) and patients with AMI and single-vessel than with multi-vessel disease (8.45 +/- 3.86 versus 10.72 +/- 3.95 pg/ml; p < 0.05). VEGF levels in AMI patients were higher than in SA patients (312.0 +/- 67.0 versus 221.0 + /- 50 pg/ml; p < 0.005). VEGF levels were higher in AMI patients with multi-vessel disease than in patients with single-vessel disease (348.74 +/- 45.23 versus 252.05 +/- 21.12 pg/ml; p < 0.005), with LVEF <40% and Killip class III-IV than in patients with LVEF >40% and Killip class I-II (338.8 +/- 51.59 versus 271.8 +/- 50.51 pg/ml; p < 0.005 and 340.71 +/- 52.94 versus 275.45 +/- 49.48 pg/ml; p < 0.05, respectively) and with chest pain > 6 h versus < 6 h (330.03 +/- 58.58 versus 292 +/- 57.53 pg/ml; p < 0.05). HsCRP concentrations in AMI patients were higher than in SA (1.24 +/- 0.47 versus 0.42 +/- 0.14; p < 0.0001). HsCRP was correlated with IL-10 (r = -0.413; p < 0.05) and VEGF (r = 0.319; p < 0.05). Acute myocardial infarction is associated with elevated VEGF levels and decreased concentration of IL-10. There is a significant correlation between levels of inflamatory markers and CHD risk factors and the function of the left ventricle on admission.     

OK-432-induced cytokines production by peripheral blood mononuclear cells]

Cytokines production by OK-432-stimulated peripheral blood mononuclear cells (PBMC) were measured to investigate the in vitro function of macrophages (M phi) and lymphocytes. PBMC (1 x 10(6) cells/ml) were cultured with OK-432 (0.05 KE/ml) for 72 hr at 37 degrees C under 5% CO2, then interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2) and soluble IL-2 receptor (sIL-2R) levels in the culture supernatants were measured by ELISA. While there was no significant differences of IL-1 beta production between patients with chronic active hepatitis type B (CAH-B) and controls, sIL-2R production (335 +/- 219 U/ml, mean +/- SD) was significantly decreased (p < 0.001) in patients with CAH-B. On the other hand, in pregnant women, production of both IL-1 beta (6.3 +/- 3.9 ng/ml, p < 0.01) and sIL-2R (300 +/- 169 U/ml, p < 0.001) were significantly lower than those in controls (13.5 +/- 3.8 ng/ml, 969 +/- 154 U/ml). These results suggest that the expression of IL-2R alpha on lymphocytes membrane is suppressed in patients with CAH-B, and that decreased M phi function is present in pregnant women.     

Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-gamma), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-gamma, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 +/- 2.8 pg/ml; controls, 3.2 +/- 0.7 pg/ml) and IFN-gamma (39.2 +/- 67.6 pg/ml; controls, 8.4 +/- 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 +/- 2.6 pg/ml), whereas IFN-gamma levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 +/- 200.4 pg/ml and 56.6 +/- 38.4 pg/ml, respectively; controls, 17.4 +/- 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 +/- 1.2 pg/ml; controls, 2.4 +/- 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 +/- 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-gamma levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-gamma may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.     

Elevated plasma amylase levels in advanced chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy: correlation with circulating interleukin-6 activity.

It has been reported that proinflammatory cytokine activation is associated with both mesenteric venous congestion and peripheral tissue underperfusion in advanced chronic heart failure. The aim of our study was to investigate if plasma amylase (as an easily approached marker of a low-grade peripheral organ injury caused by elevated systemic venous pressure and reduced cardiac output) is elevated in severe heart failure and if this elevation is correlated with cytokine and neurohormonal activation in the plasma of heart failure patients. Plasma levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), norepinephrine, and renin activity were measured in 43 severe heart failure patients (ischemic, 28; dilated, 15; left ventricular ejection fraction [LVEF] 27 +/- 3%; New York Heart Association [NYHA] classes III-IV), in 37 mild heart failure patients (ischemic, 26; dilated, 11; LVEF, 33 +/- 5%; NYHA classes I-II), and in 20 age-matched and gender-matched healthy controls. NYHA III-IV heart failure patients exhibited significantly higher plasma levels of amylase (342 +/- 19 vs. 174 +/- 13 U/L, p < 0.01), TNF-alpha (6.2 +/- 0.5 vs. 4.2 +/- 0.3 pg/ml, p < 0.01), IL-6 (5.9 +/- 0.3 vs. 4.4 +/- 0.3 pg/ml, p < 0.05), GM-CSF (21.2 +/- 2.7 vs. 4.1 +/- 0.9 pg/ml, p < 0.001), and neurohormones (both p < 0.001) compared with NYHA I-II heart failure patients and healthy controls (amylase, 165 +/- 11 U/L, p < 0.01; TNF-alpha, 2.7 +/- 0.3 pg/ml, p < 0.001; IL-6, 3.2 +/- 0.2 pg/ml, p < 0.01; GM-CSF, 3.1 +/- 0.7 pg/ml, p < 0.001). Only in NYHA III-IV heart failure patients, plasma amylase levels were significantly correlated with plasma IL-6 activity (r = 0.86, p < 0.001), plasma norepinephrine levels (r = 0.82, p < 0.001) and right atrial pressure (r = 0.52, p < 0.05). Additionally, circulating IL-6 was also significantly correlated with plasma norepinephrine (r = 0.86, p < 0.001) and right atrial pressure (r = 0.57, p < 0.01). In conclusion, plasma amylase levels were elevated in severe heart failure patients and correlated well with circulating IL-6 activation, possibly as a result of both mesenteric venous congestion and impaired peripheral tissue perfusion observed in advanced chronic heart failure. However, the lack of association between plasma IL-6 and amylase levels in mild heart failure patients indicates an independent correlation of each variable with the functional status of the disease.     

Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD).

IBD is characterized by increased serum concentrations of different cytokines. IL-10 inhibits the production of proinflammatory cytokines such as IL-1, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-gamma) and IL-6 through inhibitory action on Th1 cells and macrophages, and it is thought to be a suppressor type cytokine. In the present study we determined serum concentrations of IL-10 in patients with ulcerative colitis (UC) and Crohn's disease (CD). We measured human IL-10 by our own newly established ELISA system using PharMingen antibodies. Serum antibodies were assessed in 44 patients with UC, 40 patients with CD, and in 30 healthy controls. Human IL-10 serum levels were significantly increased in patients with active UC (144 +/- 34 pg/ml (mean +/- s.e.m.), P < 0.001) and in active CD (132 +/- 32 pg/ml, P < 0.001) compared with healthy controls (44 +/- 9.5 pg/ml). Only patients with active CD and active UC presented with significantly increased IL-10 serum levels, while patients with inactive disease did not show any significant increase. There was no statistically significant difference between IL-10 serum levels in patients with CD or UC. Compared with clinical disease activity indices there was a significant correlation between IL-10 serum concentration and CDAI in patients with CD (r = 0.45, P < 0.01) and CAI in UC patients (r = 0.39, P < 0.05). Comparing IL-10 serum levels with serum concentrations of other proinflammatory cytokines there was a significant correlation to serum levels of sIL-2R (r = 0.417, P < 0.05) and IL-6 (r = 0.387, P < 0.05) in patients with CD. Serum cytokine levels in patients with UC did not show any significant correlation to IL-10 serum concentration. IL-10 is elevated in serum of patients with active CD and UC, suggesting that IL-10 acts as a naturally occurring damper in the acute inflammatory process of IBD.     

Intravenous immunoglobulin treatment in women with recurrent abortions: increased cytokine levels and reduced Th1/Th2 lymphocyte ratio in peripheral blood

PROBLEM: The aim of this study was to investigate changes in peripheral blood Th1/Th2 cytokine levels and lymphocyte ratios after massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology. METHOD OF STUDY: Serum Th1 (IFN-gamma, TNF-alpha) and Th2 cytokine (IL-4, IL-10) levels were assessed by ELISA methods (n = 9) and peripheral blood Th1/Th2 lymphocyte ratios (n = 4) by flow cytometry before and after MIVIg treatments in women with four or more consecutive RSA. RESULTS: Pre-treatment serum IFN-gamma (0.06 +/- 0.09 pg/mL, mean +/- SD), TNF-alpha (0.21 +/- 0.45 pg/mL), IL-4 (0.70 +/- 1.16 pg/mL), and IL-10 (1.12 +/- 1.67 pg/mL) increased to 0.17 +/- 0.16 pg/mL, 0.77 +/- 0.28 pg/mL, 1.82 +/- 0.89 pg/mL, and 3.44 +/- 0.48 pg/mL, respectively, after MIVIg treatments (P < 0.05). CD4-positive IFN-gamma/IL-4 lymphocyte ratios (17.3 +/- 9.1) were reduced to 11.5 +/- 7.1 after treatment (P < 0.05). CONCLUSIONS: Massive intravenous immunoglobulin treatments increased peripheral blood cytokine levels and decreased Th1/Th2 lymphocyte ratios; thus, MIVIg treatments modify the peripheral Th1/Th2 balance.     

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: Preliminary report

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 ± 18.1 pg/ml vs. 57.2 ± 11.9 pg/ml). IL-6 level was significantly elevated (91.6 ± 46.9 pg/ml vs. 45 ± 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 ± 19 mg/l vs. 3 ± 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = –0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. On the other hand, a negative correlation between IL-10 and serum level of CRP (r = –0.76, p < 0.05), AGP (r = –0.64, p < 0.05) and ACT (r = –0.38, p < 0.05) was also observed. Moreover, these relationships were maintained when patients treated with MTX, IMG, or NSAID were analyzed independently. According to the data thus far obtained, it seems that IL-10 decreases IL-6 production, and thereby indirectly affects the acute phase response, decreasing CRP, AGP, and ACT concentration in RA patients.Abbreviations ACT -1-antichymotrypsin - AGP ₁-acid glycoprotein - APP acute phase protein - CRP C-reactive protein - CSF colony stimulating factor - IFN interferon - IL interleukin - IMG intramuscular gold - MTX methotrexate - NSAID non-steroidal anti-inflammatory drug - RA rheumatoid arthritis     

Switch from cyclosporine A to tacrolimus in renal transplant recipients: impact on Th1, Th2, and monokine responses

We showed previously that pretransplant CD4 helper defects and low in-vitro IL-10 responses predict a low risk of acute kidney graft rejection. To compare the effect of tacrolimus (Tacr) and cyclosporine A (CsA) on the humoral immune response we assessed T helper function, B cell/monocyte responses and in-vitro cytokine responses (TNF-alpha, GM-CSF, IL-1 beta, IL-2, IL-4, IL-6, IL-10) in 20 renal transplant recipients before and 3 months after they were switched from CsA to Tacr because of hyperlipoproteinemia, hirsutism, or gum hyperplasia. T helper function was assessed using a PWM-driven allogeneic coculture system of patient T cells together with control B cells. B cell/monocyte responses were determined using a PWM-stimulated allogeneic coculture system, SAC I-stimulated B-cell cultures and LPS-stimulated monocyte cultures. Immunoglobulin-secreting cell (ISC) responses were assessed in a reverse hemolytic plaque assay, and ELISA were used to determine cytokine secretion. Treatment with Tacr resulted in a decreased expression of costimulatory ligands and adhesion molecules (T cells: CD40L, p < 0.05; CD28 and CD54, p < or = 0.01; B cells: CD25, p = 0.05; CD40, p < 0.001; monocytes: CD40, p < 0.05), which coincided with decreased PHA-stimulated T cell IL-2 responses (398 +/- 153 versus 43 +/- 15 pg/ml, p < 0.05), impaired CD4 helper activity (117% +/- 22% versus 73% +/- 19%, p < 0.05) and increased CD4 suppressor activity (-120% +/- 28% versus -18% +/- 27%, p = 0.02). We observed enhanced CD4 IL-10 responses (p < 0.01) and LPS-stimulated monocyte responses (TNF-alpha, IL-1 beta, and IL-6, p < 0.005; IL-10, p < 0.05), indicating an increased humoral immune responsiveness under treatment with tacrolimus. Our data show that switching of immunosuppressive therapy from CsA to tacrolimus results in suppression of costimulatory ligands, adhesion molecules, Th1 responses and CD4 helper activity. However, enhanced humoral immune responses, Th2 and monokine responses, might have a negative impact on long-term graft function.     

Th2-type cytokines modulate IL-6 release by human bronchial epithelial cells

The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.     

苦参素对HBsAg转基因小鼠血清Th1和Th2细胞因子水平的影响

目的　探讨苦参素对HBsAg转基因小鼠外周血Th1 Th2细胞因子水平的影响。方法　HBsAg转基因小鼠分成苦参素组和对照组 ,分别每天腹腔注射苦参素注射液 2 0 0mg kg 0 2ml和生理盐水 0 2ml,共 30d。处理前后 ,检测外周血清细胞因子水平。结果　对照组处理前后γ 干扰素(IFN γ)与白细胞介素 4 (IL 4 )水平差异无显著意义 ;苦参素组处理前后IFN γ分别为 (3 10 8± 3 172 )pg ml和 (11 0 5 9± 6 971)pg ml,IL 4分别为 (2 9 0 4 5± 13 2 35 )pg ml和 (13 0 2 4± 9 0 0 2 )pg ml(均P <0 0 0 1)。处理后对照组与苦参素组IL 2分别为 (1 0 70± 0 4 4 7)pg ml和 (5 5 37± 2 887)pg ml(P <0 0 0 0 1) ;IL 10分别为 (97 2 2 6± 73 30 6 )pg ml和 (33 6 0 7± 2 3 15 4 )pg ml(P <0 0 1)。结论　在苦参素作用后 ,HBsAg转基因小鼠体内的Th1型细胞因子明显升高 ,Th2型细胞因子明显降低。这将有助于研究苦参素临床治疗乙型肝炎的机制。     

Clinical significance of serum IL-18 determination in rheumatoid arthritis

Interleukin (IL)-18 is a novel cytokine expressing at inflammatory lesion. In this study, to evaluate the clinical significance of IL-18 determination, we have examined serum IL-18, inflammation markers, sFas, and sFas-ligand concentrations in patients with rheumatoid arthritis(RA). Serum was obtained from 56 RA patients aged 35-74 years, 16 osteoarthritis (OA) patients aged 36-78 years and 178 healthy subjects aged 20-72 years and IL-18 was measured by ELISA. Serum IL-18 concentrations in RA (240.1 +/- 15.6 pg/ml, mean +/- SE) were significantly higher than OA (151.8 +/- 12.7 pg/ml, p < 0.005) and healthy controls(141.5 +/- 26.1 pg/ml, p < 0.001). Serum IL-18 levels were significantly increased in II to IV stages of RA (stage II; 218.6 +/- 31.2 pg/ml, stage III; 258.7 +/- 38.4 pg/ml, stage IV; 231.6 +/- 13.1 pg/ml) than those in OA. Furthermore, a positive correlation was observed between serum IL-18 concentration and serum Fas level in patients with RA (r = 0.472), whereas there was no significant correlation between serum IL-18 and sFas-ligand or other inflammatory markers (CRP, RF, CA-RF, IL-6, and IL-8). The present study showed that serum IL-18 level increased in RA, but it is unknown how IL-18 is involved in the pathogenesis of RA. Further study will be necessary to clarify the role of IL-18 in RA.     

Serum erythropoietin and interleukin-6 levels in hemodialysis patients with hepatitis virus infection.

The influence of hepatitis B (HBV) and hepatitis C virus (HCV) infection on blood hemoglobin (Hb) and serum erythropoietin (Epo) and interleukin-6 (IL-6) concentrations was studied in 48 anemic patients on regular hemodialysis. They were grouped as follows: (I) 19 patients whose Hb values improved after infection (Hb > 85 g/L), (II) 10 patients with persisting anemia after infection (Hb < 75 g/L), and, without hepatitis virus markers (III) 8 patients with Hb > 85 g/L and (IV) 11 patients with Hb < 75 g/L. Serum immunoreactive Epo levels were significantly higher in group I (34.4+/-47.1 U/L) than in the other groups (II, 10.8+/-6.0; III, 7.9+/-3.2; IV, 8.4+/-4.3). Serum IL-6 was higher in group I than group III (7.7+/-7.8 pg/ml vs. 3.6+/-2.4; p = 0.05) but similar to the other groups. Hb levels in group I were maximal at the time of serum alanine aminotransferase normalization. Red cell production increases as a result of elevated circulating Epo during hepatic regeneration after HBV or HCV infection.     

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.     

Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children before and after a prednisolone course.

BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the disease activity of acute asthma, changes in serum concentrations of sIL-2R and IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined in the present study. METHODS: Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in a stable condition were determined by using commercially available ELISA kits. RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2 +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P < .001). The mean concentration of serum IL-4 was higher in acute exacerbation (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL) versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was not statistically significant among the three study groups. CONCLUSIONS: This study provides further evidence that changes in serum IL-2R may serve as an objective indicator for clinical outcome of allergic asthmatic patients.     

Critically low hormone and catecholamine concentrations in the primed extracorporeal life support circuit

The first hours of extracorporeal life support (ECLS) are commonly marked by new hemodynamic instability without a known etiology. We measured hormone and catecholamine concentrations in six ECLS primed circuits immediately before joining the patient's circulation to assess a potential role of these agents in this condition. The following hormones were significantly below the lower end of the normal range for the first week of life (data are presented as mean +/- SEM): cortisol 1.95 +/- 0.15 microg/dl (p < 0.001), aldosterone 3.73 +/- 0.74 ng/dl (p < 0.05), free thyroxine 1.2 +/- 0.1 ng/dl (p < 0.05), free triiodothyronine 0.53 +/- 0.03 pg/ml (p < 0.001), thyroid stimulating hormone 0.31 +/- 0.05 microU/ml (p < 0.001), growth hormone (GH) 0.09 +/- 0.01 ng/ml (p < 0.001), estradiol 38.3 +/- 3.72 pg/ml (p < 0.001), IGF-BP1 0.95 +/- 0.1 ng/ml (p < 0.001), glucagon 26 +/- 1.2 pg/ml (p < 0.001), epinephrine 17.3 +/- 3.7 pg/ml (p < 0.001), and norepinephrine 127 +/- 27 pg/ml (p < 0.05). No dopamine was detected. Normal hormone concentrations included IGF-I, IGF-BP3, insulin, parathyroid hormone, leptin, and testosterone. Critically low concentrations of cortisol, thyroid hormones, GH, IGF-BP1, glucagon and catecholamines were measured in the ECLS circuit even though it was primed with fresh frozen plasma. These concentrations may cause significant and precipitous dilutional reductions in the patient's circulating levels immediately after connection to the ECLS circuit and hence contribute to hemodynamic instability.     

Reduced interleukin-5 production by peripheral CD4+ T cells in common variable immunodeficiency patients

We evaluated the capacity of peripheral CD4+ T helper cells in four Common Variable Immunodeficiency (CVI) patients to secrete interleukin-4 (IL-4) and IL-5. While in control CD4+ T cells, stimulated via CD3 and cultured in presence of IL-2 or IL-15, a 10 fold increased production of IL-5 (146 +/- 30; 142 +/- 25 pg/ml) was found, a 4 fold increment of this cytokine was, instead, detected in 3 out of 4 CVI patients (34 +/- 13; 39 +/- 12 pg/ml) (p < 0.05). In conclusion, the reduction of IL-5, involved in the late regulation of B cell differentiation into Ig-secreting plasma cells, may contribute to the defective antibody production in CVI patients.     

Induction of phagocyte-stimulating and Th1-promoting cytokines by in vitro stimulation of human peripheral blood mononuclear cells with Streptococcus pneumoniae

Polymorphonuclear granulocytes, which provide a major defence against Streptococcus pneumoniae infections, are attracted to and activated by various cytokines. The aim of this study was to analyse the cytokine response of human peripheral blood mononuclear cells to stimulation with S. pneumoniae. Strains belonging to serogroups 4, 6, 14, 19 or 23, were isolated from nasopharynx, middle ear fluid, cerebrospinal fluid or blood. All strains induced a marked proliferative response of the peripheral blood mononuclear cells; the stimulatory index was 34+/-11. High levels of pro-inflammatory cytokines were induced, i.e. interleukin (IL)-1beta (53+/-25 ng/ml), IL-6 (347+/-41 ng/ml) and tumour necrosis factor (TNF)-alpha (15+/-4 ng/ml). Also, chemokines and immunoregulatory cytokines including IL-8 (215+/-224 ng/ml), IL-10 (122+/-60 pg/ml), IL-12 (1195+/-648 pg/ml), interferon (IFN)-gamma (18+/-4 ng/ml) and granulocyte macrophage colony-stimulating factor (135+/-80 pg/ml) were induced. Several of these cytokines can up-regulate phagocytosis and the killing of bacteria. Interestingly, strains isolated from middle ear fluid and blood elicited significantly fewer IL-8 and significantly more IL-12 and IL-10 than strains from nasopharynx. They also induced a stronger proliferative response. Our results indicate that pneumococci are potent inducers of cytokines, especially IL-12, favouring T-helper cell type 1 (Th1) responses.     

Augmentation of leukotriene C4 production by gamma interferon in leukocytes challenged with an allergen

Leukocytes from mite-sensitive asthmatic patients were challenged with an allergen and the supernatant assayed for histamine, immunoreactive leukotriene C4 (i-LTC4), and gamma-interferon (gamma-IFN). In addition, the concentration of gamma-IFN in the plasma of patients with bronchial asthma was assayed. Significantly higher concentrations (p less than 0.01) of gamma-IFN were detected in patients' plasma (0.27 +/- 0.32 U/ml, n = 61) than in that of healthy controls (0.04 +/- 0.06 U/ml, n = 19). The leukocytes produced 7.3 +/- 6.7 ng of i-LTC4/10(6) basophils (n = 32), and histamine release was 41.1 +/- 37.1% of total histamine. There was a significant correlation (p less than 0.01) between the capacity of leukocytes to release i-LTC4 and gamma-IFN. The capacity of leukocytes to release histamine and to produce gamma-IFN was not significantly correlated (r = 0.263). About twice as much i-LTC4 was generated from leukocytes pretreated for 24 h with 0.1-1.0 U/ml of recombinant human gamma-IFN, but histamine release was not changed. Another type of IFN, alpha-IFN, did not alter the capacity of leukocytes to release histamine as well as gamma-IFN upon preincubation for 24 h at 1-1,000 U/ml. Pretreatment with 1-10 U/ml of beta-IFN slightly enhanced the capacity upon challenge with 10 ng/ml of mite allergen. The enhancing effect of gamma-IFN on i-LTC4 generation was decreased by treatment with H-7, a nonspecific inhibitor of protein kinase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum values of interleukin-10, gamma-interferon and vitamin A in female adolescents

Many studies have demonstrated that vitamin A deficiency (VAD) affects the immunomodulated response mediated by cytokines. However, these studies are controversial. The purpose of the present study was to analyze Interleukin-10, gamma-Interferon and vitamin A serum concentrations in adolescents. Seventy three female, not pregnant adolescents (15.95 +/- 1.10 years old), of a low socioeconomic condition were studied. Serum retinol was determined by HPLC using the Bieri method. International reference standards were considered to define VAD (serum retinol < 20 microg/dL), risk of VAD (20-30 microg/dL) and vitamin A sufficiency (>30 microg/dL). Serum concentrations of Interleukine-10 (IL-10) and gamma-Interferon (gamma-IFN) were detected by an ELISA method (pg/mL). The data were analyzed using the SAS/STAT statistical program; the results were presented as mean +/- Standard deviation and the differences between mean values were analyzed by the ANOVA test. The prevalence of VAD in adolescents was 6.85% (serum retinol <20 microg/dL) and 41.10% adolescents had VAD risk (20-30 microg/dL). Adolescents with VAD showed a significant increase of gamma-IFN serum concentration (p = 0.01). Correlation between serum retinol and gamma-IFN was r = -0.29 (p = 0.01). Adolescents represent a VAD risk group. Low serum levels of retinol were correlated with high levels of gamma-IFN, this cytokine has been associated with chronics inflammatory processes and it can contribute to increase the morbidity and mortality in this population.