Serum Levels Of IL-1beta Research Articles

Interferon-gamma potentiates interleukin (IL)-6 and tumor necrosis factor-alpha but not IL-1beta induced by endotoxin in the brain.

Because interferon-gamma (IFN gamma) is present in the central nervous system during neurologic diseases associated with inflammation, its effect on endotoxin-induced cytokines was studied. Cerebrospinal fluid (CSF) and serum levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF alpha), their messenger RNA expression in brain areas (hypothalamus, hippocampus, and striatum) and in spleen were evaluated 2 and 8 h after endotoxin [lipopolysaccharide (LPS), 25 microg/rat i.c.v.], IFN gamma (2.5 microg/rat i.c.v.) or after their coadministration in rats. CSF and serum IL-1beta levels were increased by LPS alone and IFN gamma coadministration did not furtherly increase them. IFN gamma potentiated LPS effect on IL-6 and TNF alpha levels in both CSF and serum. LPS and IFN-gamma coadministration did not alter IL-1beta messenger RNA expression induced by LPS in brain areas and in spleen, but it potentiated that of IL-6 and TNF alpha. The present in vivo data show that i.c.v. coadministration of LPS and IFN gamma results in a potentiation of cytokine production (IL-6 and TNF alpha) which may trigger a cascade of events relevant to neurodegenerative processes. This action is independent of IL-1beta because the production of this cytokine is not altered by IFN gamma treatment.

Cytokines derived from alveolar macrophages induce fever after bronchoscopy and bronchoalveolar lavage

As much as one-third of patients develop fever and flu-like symptoms after fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) for yet unknown reasons. The aim of the present study was to investigate factors mediating these side effects. Fifty consecutive patients with various pulmonary diseases who underwent FOB without further interventions (n = 30) or combined with BAL (n = 20) were enrolled. Serum levels of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were determined directly prior to (t0), directly after (t1), and 6 h after (t2) the procedures by ELISA. In parallel, blood cultures were drawn at t2. At to and t1, generally only low cytokine concentrations could be detected. At t2, however, significant increases of cytokine levels were found. IL-6 and TNF-alpha were significantly higher in patients after BAL than in patients after FOB. Comparing patients who developed fever (n = 12) with those who did not (n = 38), irrespective of the endoscopic procedures performed, dramatic increases of all three cytokines were detected in febrile patients that were significantly higher than in patients without fever. In the FOB group only patients who received local anesthesia by prilocaine bolus injection into the airways via the working channel of the bronchoscope developed fever and increases of IL-6 and IL-beta, whereas patients anaesthetized by inhalation of a prilocaine aerosol remained afebrile and had slight IL-6 increases only. There was a highly significant correlation between IL-6 values at t2 and the number of BAL alveolar macrophages (r = 0.98). All blood cultures remained sterile. These results indicate that fever after FOB and BAL is induced by proinflammatory cytokines derived from alveolar macrophages activated by instillation of fluid into the airways.

Elevated levels of serum interleukin-1β in combat-related posttraumatic stress disorder

Levels of serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) were assessed in 19 male patients with combat-related posttraumatic stress disorder (PTSD) in comparison to 19 age- and sex-matched healthy volunteers. Serum IL-1 beta levels (but not sIL-2R) were significantly higher (p < .001) in the PTSD patients than in the controls. IL-1 beta levels did not correlate with cortisol levels, severity of PTSD, anxiety, depressive symptoms, or alexithymia score; however, they did correlate significantly (r = .54, p < .005) with the duration of PTSD symptoms. It is possible that desensitization of the hypothalamic-pituitary-adrenal axis in chronic PTSD patients counteracts the stimulatory effect of IL-1 beta on cortisol secretion.

Serum levels of tumour necrosis factor-alpha predict response to recombinant humanerythropoietin in patients with myelodysplastic syndrome

We measured pretreatment serum levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in 25 patients with myelodysplastic syndrome receiving recombinant human erythropoietin (rhEPO) at dosages up to 300 U/kg thrice weekly for 12 weeks. Both TNF-alpha and IL-1 beta levels were measured using commercially available enzyme-linked immunoassays. A complete response (CR) was defined as a rise in untransfused haemoglobin concentrations of at least 2 g/dl or a 100% decrease in RBC transfusion requirements over the treatment period; a partial response (PR) was an increase in untransfused haemoglobin values of 1-2 g/dl or a decrease in RBC transfusion requirements equal to or greater than 50%; no response (NR) was defined as a response less than a PR. After 12 weeks of rhEPO treatment, four patients showed a CR, five patients a PR, and 16 patients NR. Serum levels of both TNF-alpha (80.5 %/- 64.8 vs 8.1 +/- 4.2 ng/l, P < 0.001) and IL-1 beta (60.4 +/- 49.9 vs 8.9 +/- 4.7 ng/l, P < 0.001) were higher in MDS patients than in a group of 28 normal controls. Responders (CR + PR) showed significantly lower serum levels of TNF-alpha than non-responders (21.6 +/- 26.2 vs 106.3 +/- 60.8 ng/l, P < 0.001), whereas IL-1 beta concentrations between those who benefited from therapy and unresponsive cases were not significantly different (39.8 +/- 48.9 vs 73.4 +/- 48.2 ng/l, P = 0.120). It is noteworthy that TNF-alpha levels were within the normal range in all responsive patients but one, whereas all non-responders presented elevated cytokine concentrations. No relationship was found between TNF-alpha or IL-1 beta values and haemoglobin levels, transfusion requirement, serum EPO or ferritin concentrations. We conclude that pre-treatment TNF-alpha levels might help to select those MDS patients who are most likely to benefit from rhEPO treatment.

Recombinant Human Erythropoietin Resistance in Hemodialysis Effects of Paired Filtration Dialysis

A percentage of hemodialysis (HD) patients are resistant to recombinant human erythropoietin (rHuEPO), a phenomenon that occurs less frequently in patients dialyzed with biocompatible membranes (M) and in peritoneal dialysis. The authors evaluated the effects of paired filtration dialysis (PFD)--a dialysis technique based on the use of an emophan M in conjunction with a polysulphone M--on erythropoiesis in HD patients resistant to rHuEPO. Twelve HD patients with anemia resistant to long-term therapy with rHuEPO (200.24 U/kg body weight three times per week intravenously for 10.2 months) were studied. Patients had been treated for an average of 46.9 months with bicarbonate HD, using cuprophan M (Phase A) and, successively, for 12 months by PFD (Phase B). The following parameters were evaluated monthly: 1) hemoglobin and hematocrit values; 2) serum levels of erythropoietin (EPO); and 3) serum levels of interleukin (IL)-3, IL-6, IL-10, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). At the end of Phase A and Phase B, patients underwent bone marrow biopsies to evaluate 1) bone marrow burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) proliferative capacity, and 2) bone marrow mononuclear cell EPO-receptor (EPO-R) number. During Phase B, there was a progressive rise in hematocrit and hemoglobin values, so that within the sixth month, the rHuEPO dose was reduced to 80 +/- 15 U/kg body weight three times per week. At the same time, an increase in serum IL-3, IL-6, and IL-10 levels was seen, whereas serum IL-1 beta, TNF-alpha, and IFN-gamma levels decreased. This was accompanied by a rise in BFU-E and CFU-E growth and in bone marrow mononuclear cell EPO-R number. During Phase B, after the dialysis session, serum EPO levels increased by about 30% in comparison with pre dialysis values, whereas during Phase A they decreased by about 14%. In HD patients, EPO resistance may caused either by absorption of rHuEPO to the cuprophan M, or an increased release of cytokines that inhibit erythropoiesis, such as IL-1 beta, TNF-alpha, and IFN-gamma, and to a decrease in stimulatory cytokines such as IL-3, IL-6, and IL-10. These negative phenomena are reversed by the use of biocompatible dialysis techniques such as PFD.

An assessment of peripheral immunity in patients with sarcoidosis using measurements of serum vitamin D3, cytokines and soluble CD23.

The aetiology of the peripheral anergy in sarcoidosis is unclear. To investigate this further we measured the serum levels of several factors important in different aspects of immune regulation to obtain a profile of those factors which promote and inhibit immune activation in sarcoidosis. Thirty-seven patients with sarcoidosis and 20 healthy controls of similar sex and age comprised the study group. Serum IL-10, interferon-gamma (IFN-gamma), soluble CD23 (sCD23), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1beta and tumour necrosis factor-alpha (TNF-alpha) were measured using in-house ELISAs. Vitamin D3 was measured using a radioreceptor assay. Serum levels of sCD23 and IL-10 were significantly elevated in patients with sarcoidosis relative to controls (median 13.9 versus 9.5 arbitrary units/ml, P<0.01 for sCD23, and 9.6 versus 5.0 pg/ml, P<0.04 for IL-10). Regardless of steroid therapy or disease activity, serum levels of IFN-gamma, TNF-alpha, IL-1beta, GM-CSF and IL-8 were no different in patients with sarcoidosis and controls. Vitamin D3 levels were significantly higher in patients with sarcoidosis versus normal controls (medians 78.0 versus 56.0, P<0.001), active sarcoidosis (n = 20) versus inactive disease (n = 17) (medians 81.5 versus 66.0, P<0.03) and active sarcoidosis versus controls (medians 81.5 versus 56.0, P<0.0002). The levels were no different between patients with inactive sarcoidosis and controls. We suggest that IL-10 and vitamin D3 may contribute to the peripheral anergy in sarcoidosis. The elevated serum sCD23 suggests an increase in peripheral humoral immunity. Consistent with a quiescent peripheral immune system, factors capable of monocyte/macrophage activation (TNF-alpha, IFN-gamma, GM-CSF and IL-8) were not elevated in the peripheral circulation.

Serum levels of interleukins, growth factors and angiogenin in patients with endometrial cancer.

The purpose of this work was to study changes in serum levels of interleukins, growth factors and angiogenin during different stages of endometrial cancer progression. Serum levels were assayed by enzyme-linked immunosorbant assay in 59 women with stages I-IV of endometrial cancer (study subjects: stage I, n = 20; stage II, n = 8; stage III, n = 5; stage IV, n = 6) and compared to the serum levels in 20 women without cancer as control subjects. Patients with endometrial cancer had varied serum levels of interleukins and growth factors. There was a significant increase in serum levels of angiogenin in all stages of tumor progression. Levels of interleukin-8 (IL-8), IL-10 and transforming growth factor beta (TGF beta) were significantly elevated in patients with stages I and II carcinoma. The serum levels of tumor necrosis factor alpha (TNF alpha), granulocyte/macrophage-colony-stimulating factor, basic fibroblast growth factor (BFGF), IL-7 and IL-2 were significantly elevated in patients with stages II and III carcinoma and the serum level of tumor necrosis factor beta (TNF beta) was slightly elevated in patients with stage II carcinoma only. The serum levels of IL-1 alpha, IL-1 beta and IL-6 were not elevated in endometrial cancer patients in any of the clinical stages. The results showed that progression of endometrial cancer is associated with increased serum levels of cytokines, growth factors and angiogenin, which possibly amplify angiogenesis during different clinical stages.

Severity and Mortality of Experimental Pancreatitis Are Dependent on Interleukin-1 Converting Enzyme (ICE)

Interleukin-1 beta (IL-1 beta) is produced in large amounts during acute pancreatitis and is believed to play a role in disease progression. Because secretion of IL-1 beta is dependent on intracellular processing of pro-IL-1 beta by IL-1 converting enzyme (ICE), we aimed to determine the efficacy of a novel ICE inactivator (VE-13045) in inhibiting secretion of active IL-1 beta in vivo and if the loss of ICE activity would affect the severity and mortality of experimental pancreatitis. Severe hemorrhagic pancreatitis was induced in adult rats by infusion of bile acid into the pancreatic duct. Animals were randomized to receive VE-13045 or vehicle before induction of pancreatitis. To confirm our findings and to ensure that the results were not model dependent, a second series of experiments was conducted using mice possessing a homozygous knockout of the ICE gene in which lethal pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented diet. The severity of pancreatitis was assessed for both experiments by standard surrogate markers, blind histologic grading, and serum IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) levels. Pancreatic IL-1 beta mRNA induction was assessed by differential RT-PCR. Acute pancreatitis was associated with a 120-fold increase in IL-1 beta mRNA, which was not affected by ICE inhibition or gene deletion. Cytokine processing and secretion were affected, as evidenced by decreased serum levels of IL-1 beta and TNF-alpha (p < 0.001) in all animals with an inactive ICE enzyme. This lack of cytokine production increased survival from 32% to 78% following bile salt pancreatitis (p < 0.01) and from 24% to 80% following diet-induced pancreatitis (p < 0.005). Both ICE-defective groups demonstrated decreased pancreatic necrosis, edema, inflammation, wet weight (all p < 0.05), and amylase and lipase (p < 0.01). In vivo blockade or genetic deletion of ICE inhibits pancreatitis-induced secretion of proinflammatory cytokines without altering IL-1 mRNA production and is associated with decreased pancreatitis severity and dramatic survival benefits.

Enhanced expression of cytokines may play a fundamental role in the mechanisms of immunologically mediated recurrent spontaneous abortion.

To determine circulatory levels of IL-1 beta, TNF alpha, IFN-gamma and Neopterin in immunologically mediated recurrent abortion. Blood samples were withdrawn from both groups of first trimester recurrent abortion and controls for the determination of serum IL-1 beta, TNF alpha, IFN-gamma by the corresponding IRMA and serum neopterin by a double antibody RIA. Department of Obstetrics & Gynecology, Cairo University Hospitals. Thirty pregnant women in their first trimester who presented with inevitable abortion with history of at least 3 prior spontaneous consecutive abortions, in addition to twenty-three pregnant women in their first trimester presented with their first miscarriage due to chromosomal anomalies (controls). Every attempt was made to eliminate the possible known contributing factors of recurrent abortion except for the presence of cervical mucus sperm antibodies which were present in 24 out of 30 cases. None. Serum IL1 beta, TNF alpha and IFN-gamma levels of the abortion group were significantly elevated when compared to the corresponding levels of controls. The incidence of abnormal high values of these cytokines varied between 40 to 70%. There was no significant difference of serum neopterin between abortion and control groups. The increase of IFN gamma, the most active principle inducing neopterin release, was below the concentration needed for neopterin stimulation. In view of the proven findings that cytokines do have detrimental effects on implantation, trophoblast proliferation, embryo development and fetal survival, our results suggest a potential mechanism of immunologic recurrent abortion which involves the secretion of IL-1 beta, TNF alpha, IFN gamma and other cytokines by activated endometrial lymphocytes and macrophages in response to either trophoblast or sperm antigens and these cytokines could partially defuse or penetrate into the systemic circulation.

Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production.

To elucidate the molecular mechanisms regulating the anti-inflammatory activities of recombinant human (rh)IL-11, the ability of rhIL-11 to reduce serum levels of inflammatory mediators such as TNF-alpha, IL-1beta, IL-12, and IFN-gamma in LPS-treated mice and to down-regulate macrophage function in culture was investigated. In a mouse model of endotoxemia, pretreatment with rhIL-11 blocked LPS-induced elevation of TNF-alpha, IL-1beta, and IFN-gamma serum levels, but had no effect on IL-12 p40, IL-6, or IL-10 serum levels. The effects of rhIL-11 on the production of inflammatory mediators in vivo may occur in part through direct interactions with macrophages. rhIL-11 pretreatment of thioglycollate-elicited peritoneal macrophages resulted in greater than 60% inhibition of LPS-induced production of TNF-alpha, IL-1beta, IL-12 p40, and nitric oxide. The activity of rhIL-11 was not mediated through induction of IL-10, IL-6, or TGF-beta1. These results indicate that the ability of rhIL-11 to modulate the inflammatory response is not dependent on known anti-inflammatory cytokines and substantiate a role for this cytokine in the attenuation of inflammatory conditions.

Increased levels of nitrite in the sera of children infected with human immunodeficiency virus type 1.

Nitric oxide (NO) is a newly discovered gas that plays an important role in cell communication and host resistance to infection. The production of NO was examined in the sera of seven children infected with human immunodeficiency virus type 1 (HIV-1) and in the sera of 14 children who became seronegative for HIV-1 during the first year of life. In addition, we determined serum levels of various cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and gamma interferon (IFN-gamma), inasmuch as these cytokines are potent inducers of NO production. Production of NO, detected as circulating serum levels of nitrite, was measured with use of the Griess reagent. Serum levels of cytokines were determined by enzyme immunoassay. Increased serum levels of nitrite were observed in children with HIV-1 infection (0.4 +/- 0.2 mumol/L; P = .013), and in those who became seronegative for HIV-1 during the first year of life (0.5 +/- 0.3 mumol/L; P = .04). Furthermore, serum levels of IL-1 beta and TNF-alpha were significantly elevated in children with HIV-1 infection (37.5 +/- 23.6 pg/mL and 91.2 +/- 45.1 pg/mL, respectively). Prophylactic administration of intravenous immune globulin provoked a significant decrease of circulating levels of nitrite in children with HIV-1 infection. In conclusion, NO may play a role as a cytostatic or cytotoxic factor for invading microorganisms, and thus it is probably involved in limiting and/or eradicating infection.

Serum interleukin-1 beta in neonatal sepsis.

Serum levels of interleukin-1 beta (IL-1 beta) in newborn infants with septicaemia were measured and possible relationships between the clinical course of the infants, causative micro-organisms and IL-1 beta levels were investigated in a prospective study. The study groups comprised 49 newborn infants (25 mature, 24 premature) with proven sepsis and 40 healthy newborn infants (20 mature, 20 premature). Serum IL-1 beta levels were measured using the IL-1 beta immunoradiometric assay. The levels were found to be lower in neonates with sepsis (median 0.1 pg/ml) than in healthy controls (median 27.9 pg/ml) (p < 0.001). Non-significant trends towards lower levels were observed in children with shock and in non-survivors. No correlation was found between IL-1 beta and postnatal age, gestational age or the study weight of the patients. There was no significant difference in the serum IL-1 beta level in septic patients infected with Gram-positive bacteria and those infected with Gram-negative bacteria. The results show that the concentration of IL-1 beta is significantly decreased in preterm and term neonates with sepsis.

Overproduction of Proinflammatory Cytokines Imbalanced by Their Antagonists in POEMS Syndrome

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon-gamma [IFN-gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4, IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta, TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL-13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF-alpha) associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious effects of cytokines.

Impact of interferon-gamma receptor deficiency on experimental Staphylococcus aureus septicemia and arthritis.

The role of IFN-gamma in the regulation of host resistance of Staphylococcus aureus was studied using IFN-gamma receptor-deficient (IFN-gamma R-/-) mice in a model of S. aureus-induced septicemia and arthritis. IFN-gamma R-/- mice and wild-type controls were inoculated intravenously with a toxic shock syndrome toxin-1-producing S. aureus LS-1 strain. IFN-gamma R-/- mice displayed significantly more frequent and more severe arthritis compared with wild-type littermates (p < 0.01) throughout the course of infection. Notably, IFN-gamma R-/- mice developed severe sepsis with high mortality early after the inoculation with staphylococci. However, the mortality of wild-type mice became significantly higher at later stages of the disease compared with IFN-gamma R-/- mice (p < 0.05). This differential outcome of sepsis-related mortality was associated with deficiencies of bacterial elimination from blood and parenchymatous organs and correlated well to serum levels of IL-6 and spleen IL-1 beta and TNF-beta mRNA expression. Thus, bacterial growth and proinflammatory cytokines IL-1 beta, TNF-beta, and IL-6 were higher at the early stage of infection in IFN-gamma-/- mice but increased at the later stage in wild-type littermates. Our data indicate that the absence of IFN-gamma R leads to harmful as well as beneficial effects in S. aureus infection, depending on the stage of the disease and the localization of the infection.

Increased serum interleukin-1 beta during treatment of hyperthyroidism with antithyroid drugs.

Serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) levels were examined in patients with hyperthyroidism due to Graves' disease (GD) and toxic nodular goitre (TNG) before and during antithyroid drug therapy. A total of 32 patients were studied; 23 patients (14 with GD and nine with TNG) were in a hyperthyroid state (group A) and nine patients (four with GD and five with TNG) were in a euthyroid state, under carbimazole or methimazole treatment (group B). Ten hyperthyroid patients from group A (seven with GD and three with TNG) were also examined while euthyroid on treatment (Subgroup A). Serum was taken from all patients for the measurement of sIL-2R, IL-1 beta, total T4 (TT4), total T3 (TT3) and TSH concentrations. The results were compared with those from 30 normal controls. Serum sIL-2R levels were higher in Group A (671.3 +/- 74.0 U mL-1, mean +/- SE), than in Group B (214.1 +/- 61.8 U mL-1) and controls (149 +/- 14.8 U mL-1), P < 0.001. Similarly, the subgroup of 10 patients had higher levels of sIL-2R during the hyperthyroid phase than while euthyroid (P < 0.001). There was a positive correlation between sIL-2R values and levels of T4 and T3. In contrast, serum IL-1 beta levels were higher in Group B patients (197.5 +/- 39.2 pg mL-1) compared with those in Group A (66.5 +/- 17 pg mL-1, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmunity induction by human T cell leukemia virus type 1 in transgenic mice that develop chronic inflammatory arthropathy resembling rheumatoid arthritis in humans.

We recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T cell leukemia virus type 1 genome. In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated. Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular immune response to IIC as well as that to heat shock proteins were activated. Moreover, these mice became immunologically responsive to exogenously administered IIC and developed arthritis, in contrast to their nontransgenic littermates, which showed little response to IIC. Taken together, the results suggest that human T cell leukemia virus type 1 can cause immune system hyperreactivity and induce autoimmunity. The possibility that elevated cytokine and/or MHC gene expression are involved in the development of autoimmunity and arthropathy are discussed.

Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is characterized by the proliferation of smooth-muscle cells, fibroblasts, and endothelial cells in the walls of small pulmonary arteries. In order to evaluate a role for proinflammatory cytokines in this process, we studied the concentration of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the serum of 29 patients with severe PPH referred to our center for lung transplantation. Results were compared with those obtained in 15 normal controls and nine patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD-PH). TNF alpha serum levels were within the normal range in each group. This contrasted with increased IL-1 beta serum levels in severe PPH (118 +/- 36 pg/ml, mean +/- SEM) as compared with controls (3 +/- 1 pg/ml, p < 0.001) or COPD-PH patients (3 +/- 1 pg/ml, p < 0.001). IL-6 serum concentrations were also higher in severe PPH (66 +/- 20 pg/ml) than in controls (14 +/- 6 pg/ml, p < 0.01). This study demonstrates increased serum levels of IL-1 beta and IL-6 in severe PPH, and suggests a role for proinflammatory cytokines in PPH.

Kinetics of serum cytokines in adults undergoing peripheral blood progenitor cell transplantation.

We investigated the serum cytokine levels (G-CSF, GM-CSF, IL-1 beta, IL-3 and IL-6) using an ELISA in 14 patients with haematological malignancies undergoing peripheral blood progenitor cell transplantation (PBPCT). Serum G-CSF levels in all patients rose immediately after PBPCT, then gradually decreased as the neutrophil counts began to rise. No detectable serum levels of GM-CSF or IL-1 beta were observed, but serum levels of IL-3 rose transiently immediately following PBPCT. Serum levels of IL-6 rose transiently during a fever in four patients. These observations suggest that G-CSF and IL-3 may contribute to the early haemopoietic reconstitution in PBPCT.

Circulating levels of cytokines that modulate bone resorption: effects of age and menopause in women.

Interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are cytokines with potent bone-resorbing effects; some of these biologic effects are opposed by interleukin-1 receptor antagonist (IL-1ra). In vitro and animal model studies suggest that these cytokines are paracrine mediators of the increased bone resorption associated with estrogen deficiency, and increases in their production also could contribute to age-related bone loss. Therefore, we measured serum concentrations of these cytokines in 80 normal women who were 24-87 years old. IL-6 concentration correlated highly with age (p < 0.001) and increased three-fold during life. However, multiple-regression analysis showed no significant correlation between serum IL-6 levels and menopausal status, serum estradiol concentration, or markers for bone turnover (serum bone alkaline phosphatase, osteocalcin, carboxyl-terminal telopeptide of type I collagen, or 24 h urinary free pyridinoline excretion). Serum IL-1 alpha, IL-1 beta, or IL-1ra level did not change with age and, by multiple-regression analysis, did not correlate with markers of bone turnover, except IL-1ra weakly with ICTP. We found no relationship between bone-resorbing cytokines and ovarian function. Although the large age-related increase in serum IL-6 concentration could contribute to age-related bone loss, the lack of correlation with markers for bone turnover argues against this. However, based on the strong evidence in experimental animals that these cytokines are involved in estrogen action on bone, further studies in humans are warranted.

Serum levels of interleukin-1β and interleukin-6 in patients with chronic pancreatitis

To investigate the role played by cytokines in chronic pancreatitis, we examined serum levels of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in 33 patients with definitively diagnosed chronic pancreatitis. All the patients, who had received either no treatment or only digestive enzyme products for their chronic pancreatitis, had significantly elevated serum IL-1 beta levels (38.5 +/- 28.8 pg/ml, mean +/- SD), compared to normal controls (16.0 +/- 6.7 pg/ml; P < 0.01); however they showed no changes in serum IL-6 levels. Changes in IL-1 beta and IL-6 serum levels were not correlated with the etiological features of pancreatitis or with complications due to liver diseases. Serum IL-1 beta and IL-6 levels were also not correlated with the activity of any pancreatic enzymes in blood or urine. However, in the patients with chronic pancreatitis, serum IL-6 levels were correlated with C-reactive protein (CRP), whereas serum IL-1 beta levels were not correlated with CRP or with erythrocyte sedimentation rate. These results suggest that serum IL-1 beta is involved in the progression and reduction of chronic inflammation of the pancreas, and that the serum IL-1 beta level may be useful as a marker for chronic pancreatitis.