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K Brismar

Publications and source records attributed to K Brismar.

At least 19 recordsLinked to original sources
PubMed2000

Tamoxifen-induced cell death in malignant melanoma cells: possible involvement of the insulin-like growth factor-1 (IGF-1) pathway.

Recent data indicate that the estrogen receptor (ER) blocker tamoxifen (TAM) can induce cell death in malignant melanoma cells. However, as shown in the present study and several other studies melanoma cells usually do not express classical ERs. In the present study we investigated whether the cytotoxic effect of TAM on melanoma cells could depend on interference with the expression or function of the insulin-like growth factor-1 receptor (IGF-1R), a plasma membrane receptor important for cell survival in this tumor cell type. Several melanoma cell lines were included in the analysis. Administration of TAM at a concentration of 15 microm or more resulted in cell death of the melanoma cells within 48 h. TAM treatment was correlated to a slight to moderate inhibition of IGF-1 binding to IGF-1R. Since it has been reported that TAM can increase the release of IGF binding proteins (IGFBPs) we then investigated whether this mechanism could underly the decreased IGF-1 binding. However, we could demonstrate that the amount of released IGFBPs were unchanged or decreased in TAM-treated cells. Whereas TAM did not have any strong effect on IGF-1 binding and the expression of IGF-1R at the cell surface, it was was found to efficently block tyrosine phosphorylation of IGF-1R beta-subunit. Taken together, our data suggest that TAM-induced cytotoxicity of malignant melanoma cells can be due to inactivation of IGF-1R.

Antineoplastic Agents, Hormonal↗
PubMed2000

Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment.

OBJECTIVES: We investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized, serial angiographic trial of a fibrate compound, demonstrated that progression of focal coronary atherosclerosis in young patients after infarction could be retarded by bezafibrate treatment. METHODS: The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1, as well as on basal and postload glucose and insulin levels, were examined, and on-trial determinations were related to the angiographic outcome measurements. RESULTS: Bezafibrate treatment resulted in a significant reduction of serum IGF-I levels, both at two and five years, and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter (r = 0.25, p < 0.05) and mean segment diameter (r = 0.29, p < 0.05). In contrast, none of the available indexes of insulin resistance (homeostasis model assessment estimate, basal and postload plasma insulin concentrations and serum IGFBP-1 levels) were related to the angiographic changes, nor were they significantly affected by bezafibrate treatment. Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease (CAD) progression was independent of baseline angiographic score, age, body mass index, serum lipoprotein and plasma fibrinogen concentrations and measures of glucose-insulin homeostasis. CONCLUSIONS: IGF-I could be implicated in the progression of premature CAD, and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis.

Adult↗
PubMed2000

The hyperinsulinaemic-euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects.

To examine the reproducibility of the hyperinsulinaemic-euglycaemic clamp technique at mid-physiological hyperinsulinaemia, seven healthy subjects ¿age 50 (25, 59) years [median (range)], body mass index 23.1 (20.8, 25.5) kg.m(-2)¿ were investigated with three 2 h hyperinsulinaemic (60 micromol.l(-1))-euglycaemic (4.5 mmol.l(-1)) clamps performed 48 h and 14 days apart respectively. The third clamp was prolonged to 8 h in order to examine effects on glucose disposal during prolonged clamps. The glucose infusion rates (GIRs) during the three 2 h clamps were 7.41 (4.28, 10.96), 7.26 (5.38, 11. 02) and 6.63 (4.42, 10.3) mg.kg(-1).min(-1), with a median intra-individual coefficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly variable gradual increase in GIR was observed, reaching a plateau between 4 and 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P<0.05). This increase was correlated inversely with the GIR between 1 and 2 h (r=-0.82; P<0.05), and directly with age (r=0.86; P<0.05). Carbohydrate oxidation measured by indirect calorimetry was stable during the repeated 2 h clamps and the 8 h clamp. Endogenous glucose production measured by infusion of [6, 6-(2)H(2)]glucose was suppressed during the 8 h clamp. The 2 h hyperinsulinaemic-euglycaemic clamp is reproducible at a mid-physiological range of hyperinsulinaemia. If prolonged, it results in a delayed increase in non-oxidative glucose disposal, which is most pronounced in subjects with low insulin sensitivity. The findings underline the importance of selecting age-matched controls in studies of insulin resistance.

Adult↗
PubMed2000

Insulin-like growth factor (IGF)-1 and IGF-binding protein-1 concentrations in serum of normal subjects after alcohol ingestion: evidence for decreased IGF-1 bioavailability.

OBJECTIVE: Both insulin-like growth factor (IGF)-1 and insulin-like growth factor-binding protein (IGFBP)-1 are synthesized by the liver. It is well known that chronic alcohol abuse impairs liver function, but less is known about how an acute intake of moderate quantities of alcohol affects hepatic production of IGF-1 and IGFBP-1. The objective of the present investigation was to study this issue by measuring serum levels of IGF-1 and IGFBP-1 in normal subjects before, during and after ingestion of a moderate dose of ethanol. SUBJECTS AND DESIGN: Eight healthy subjects were tested on two occasions. On one occasion (experiment A), three 150-ml doses of ordinary drinking-water were given at 08.00, 09.30, and 11.00 h. On another occasion (experiment B), three 150-ml drinks of diluted ethanol were given instead of water. Each drink contained 0.45 g ethanol/kg b.w. Experiments A and B were performed in random order, 1 week apart. Blood samples were collected before, during and after the drinks over a period of 7 h (08.00-15.00 h). One blood sample was also drawn at 08.00 h the following day. MEASUREMENTS: Blood glucose and serum concentrations of ethanol, insulin, growth hormone (GH), IGF-1 and IGFBP-1 were determined. RESULTS: When alcohol had been ingested, the serum ethanol concentration rose to a peak value of 28.6 +/- 0.9 mmol/l (mean +/- SEM). The serum IGF-1 level declined significantly toward the end of the 7-h period. The serum IGFBP-1 level increased promptly in response to ethanol, and reached a maximum 2.7 times above basal as the ethanol level peaked. Neither IGF-1, nor IGFBP-1 levels changed significantly after water intake. The IGF-1 : IGFBP-1 ratio declined markedly after ethanol (from 15.7 +/- 3.9 to 3.9 +/- 0.6; P < 0.01), but not after water intake. The blood glucose and serum levels of insulin and GH were unaffected by both ethanol and water. CONCLUSIONS: Ingestion of moderate amounts of alcohol by healthy individuals results in an acute and profound increase in the serum IGFBP-1 level and a protracted and less powerful decline in the IGF-1 level. The mechanism behind the IGFBP-1 increase is probably a direct effect on the liver, since neither insulin, nor glucose or GH concentrations changed significantly in response to the ethanol challenge.

Adult↗
PubMed1999

Nutritional status, insulin-like growth factor-1 and quality of life in elderly women with hip fractures.

AIM: To evaluate nutritional status and its relation to cognitive and physical function and quality of life in elderly female patients with hip fractures. METHODS: Nutritional status was assessed in 42 women (80+/-7 years old) using the body mass index (BMI), triceps skin fold, arm muscle circumference and serum levels of insulin-like growth factor (IGF-1) and its binding protein (BP) IGFBP-1. Handgrip strength was measured. The Short Portable Mental Status Questionnaire was used to assess cognitive function and the Nottingham Health Profile to asses quality of life. RESULTS: Low BMI (<== 20) and reduced IGF-1 and IGFBP-1 levels were detected in 50% of the patients. BMI correlated with IGF-1 (p<< 0.02) and with hand grip strength (P<< 0.001). Hand grip strength correlated with arm muscle circumference (P<< 0.05). Cognitive dysfunction was detected in 18% of the patients, and a correlation was found between cognitive function and BMI (P<< 0.01). The Nottingham Health Profile assessment indicated a lower quality of life in underweight patients as compared to others (P<< 0.05). CONCLUSIONS: Half of the elderly women with hip fractures displayed signs of protein-energy malnutrition. Underweight was associated with reduced serum levels of IGF-1, muscle fatigue, cognitive dysfunction and a low quality of life rating, i.e. a cluster of factors which may unfavourably influence the postoperative course in a large proportion of hip fracture patients.

Activities of Daily Living↗
PubMed1999

Effects of oxytocin on the IGF-axis and some gastrointestinal hormones in ad libitum fed and food-restricted female rats.

The aims of this study were to investigate if administration of oxytocin to ad libitum fed and food-restricted female rats affects weight gain, body fatness, the IGF-axis, and some vagally mediated gastrointestinal hormones, such as gastrin, cholecystokinin (CCK) and somatostatin. Ad libitum fed and food-restricted (receiving 70% of the food intake of the ad libitum fed group) female rats were injected subcutaneously, once a day, for 10 days, with saline (control) or oxytocin (1 mg kg-1 bodyweight). The animals were killed 5 days after the last injection. Oxytocin-treated food-restricted females had more body fat and lower plasma levels of IGF-I, IGFBP-1 and IGFBP-3 compared with saline-treated counterparts. Oxytocin-treated ad libitum fed rats also had lower plasma levels of IGFBP-1 but contained less body fat, compared with saline-treated counterparts. There was no effect of oxytocin treatment on body weight or weight gain in either of the feeding groups. Except for gastrin, which was lower, there was no effect of oxytocin on the gastrointestinal hormones studied. The results indicate that oxytocin treatment influences fat deposition and the IGF-axis in female rats, but that the results are dependent on the nutritional status of the animal.

Animals↗
PubMed1999

Anti-cardiolipin antibodies and circulating immune complexes in type 1 diabetes mellitus: increased prevalence and relation to vascular complications.

Anti-cardiolipin antibodies, oxidatively modified low-density lipoproteins (oxLDL) and circulating immune complexes are humoral factors that have been linked to vascular damage. To analyse their possible role in the vascular complications in type 1 diabetes mellitus, we investigated patients with and without vascular complications (retinopathy, nephropathy, polyneuropathy, foot ulcers). The patients were matched for age, sex and duration of diabetes. The patients were also compared with 102 healthy individuals. Anti-cardiolipin antibodies of IgG and IgA type were more common in patients compared with healthy individuals. There was no difference between patients with and without vascular complications. There was no increased prevalence of IgM anti-cardiolipin antibodies, but the levels of these antibodies were higher in patients with vascular complications compared with patients without complications and controls. Eighty-three percent of patients had circulating immune complexes in comparison with 5% of healthy individuals. Such complexes were more common in patients with complications. Both the prevalence and the levels of immune complexes were higher in patients with null alleles of complement factor C4. Patients with vascular complications had higher prevalence of C4A than of C4B null alleles. Anti-cardiolipin antibodies were present in higher relative concentrations in immune complex form than in serum in all six patients analysed. There was no increased prevalence of antibodies against oxidatively modified LDL in the patients. The higher prevalence and levels of anti-cardiolipin antibodies and circulating immune complexes in patients with vascular complications suggests that these humoral factors might be involved in the vascular complications of type 1 diabetes mellitus.

Adult↗
PubMed1999

Splanchnic exchange of insulin-like growth factor binding protein-1 (IGFBP-1), IGF-I and acid-labile subunit (ALS) during normo- and hyper-insulinaemia in healthy subjects.

OBJECTIVE: The main source of circulating IGF-I, insulin like growth factor binding protein-1 (IGFBP-1) and acid-labile subunit (ALS) is considered to be the liver, but their production rates have not been determined in healthy individuals. Thus, the splanchnic exchange of IGFBP-1, IGF-I, ALS and glucose were studied. STUDY DESIGN: In five overnight fasting healthy, normal weight men (mean age 29 +/- 1 years) blood samples were taken from a hepatic vein, a brachial artery and a peripheral vein in the basal state and during 3 h i.v. infusion of insulin (1.0 mU/kg/min). Normoglycaemia was maintained with a variable glucose infusion and splanchnic blood flow was determined using a constant rate indicator infusion technique. RESULTS: The basal net splanchnic glucose output amounted 0.96 +/- 0. 09 mmol/min and the splanchnic production of IGFBP-1 was 7 +/- 2 microg/min. There was a net splanchnic uptake of IGF-I (7 +/- 2 microg/min) in the basal state, while no significant splanchnic exchange of ALS was found. During the insulin infusion, insulin concentration increased from 78 +/- 12 to 660 +/- 30 pmol/l, resulting in a complete inhibition of splanchnic glucose production after 40 min of infusion. Splanchnic IGFBP-1 production rose initially to 13 +/- 4 microg/min (P < 0.05) and then gradually decreased and was completely inhibited at 180 min (P < 0.05). Insulin infusion influenced neither ALS nor IGF-I splanchnic exchange. CONCLUSION: Splanchnic production of IGFBP-1 in the basal state was demonstrated and it is completely inhibited after 180 min of hyperinsulinaemia. In contrast to what is generally held, there was no net splanchnic production of IGF-I in the basal state or during insulin stimulation.

Adult↗
PubMed1999

Malignant human renin producing paraganglionoma-localization with 123I-MIBG and treatment with 131I-MIBG.

A 22-year-old woman presenting severe hypertension and hypokalaemia is described. Initial evaluation showed a large tumour localized at the position of the left adrenal gland. Subsequent surgery temporarily relieved all signs and symptoms caused by the tumour. The symptoms relapsed after a 2-year disease-free interval. At re-evaluation, the tumour was shown to produce an uncontrolled secretion of renin, thus triggering aldosterone-dependent hypertension. This report describes the diagnosis, treatment and clinical course of this unique patient with a malignant paraganglionoma of adrenal origin.

3-Iodobenzylguanidine↗
PubMed1999

Effects of oxytocin treatment early in pregnancy on fetal growth in ad libitum-fed and food-restricted rats.

The effects of oxytocin on fetal and placental growth and on maternal weight gain and accumulation of body fat were studied in ad libitum-fed and food-restricted (receiving 70% of the food intake of the ad libitum-fed group) pregnant rats. Further, a possible role of the IGF axis in mediating oxytocin-induced changes was assessed. Pregnant rats were injected subcutaneously once a day during gestational d 1-5 with saline or oxytocin (1 mg/kg). Ad libitum-fed oxytocin-treated pregnant rats had higher circulating levels of IGF-I, larger placentas, fetuses, and newborn pups and contained less body fat at the end of pregnancy. In food-restricted dams, oxytocin-treatment had no effect on fetal and placental growth. Additionally, food restriction attenuated the normal increase in IGF binding protein-3 protease proteolysis during pregnancy. The results show that oxytocin may affect maternal adaptations to pregnancy and stimulate fetal growth. We suggest that this effect may be mediated by increased IGF-I in ad libitum-fed animals, whereas food restriction may block this effect by resulting in low levels of circulating IGF-I and by attenuating the pregnancy-associated increase in IGF binding protein-3 protease activity and, thereby, further compromise IGF bioavailability.

Adipose Tissue↗
PubMed1999

Transcutaneous oxygen tension and toe blood pressure as predictors for outcome of diabetic foot ulcers.

OBJECTIVE: The present study was undertaken to compare the predictive values of transcutaneous oxygen tension (TcPO2) and toe blood pressure (TBP) measurements for ulcer healing in patients with diabetes and chronic foot ulcers. RESEARCH DESIGN AND METHODS: Investigated prospectively were 50 diabetic patients (37 men) with chronic foot ulcers. The age was 61 +/- 12 (mean +/- SD), and the diabetes duration was 26 +/- 14 years. TBP (mmHg) was measured in dig I and TcPO2 (mmHg) at the dorsum of the foot. Ulcer healing was continuously evaluated by measuring the ulcer area every 4-6 weeks. After a follow-up time of 12 months, the patients were divided into three groups according to clinical outcome: healed with intact skin, improved ulcer healing, or impaired ulcer healing. RESULTS: Of the 13 patients who deteriorated, 11 had TcPO2 < 25 mmHg, while 34 of the 37 patients who improved had TcPO2 > or = 25 mmHg. The sensitivity and specificity for TcPO2 were 85 and 92%, respectively, when a cutoff level of 25 mmHg was used for determination of outcome of ulcer healing (healing or nonhealing). The corresponding values for TBP at 30 mmHg were 15 and 97%. Measurement of TcPO2 provided a higher positive predictive value (79%) than TBP (67%). CONCLUSIONS: The results indicate that TcPO2 is a better predictor for ulcer healing than TBP in diabetic patients with chronic foot ulcers, and that the probability of ulcer healing is low when TcPO2 is < 25 mmHg.

Blood Pressure↗
PubMed1998

Pronounced skin capillary ischemia in the feet of diabetic patients with bad metabolic control.

Skin capillary circulation is impaired during postocclusive reactive hyperaemia (PRH) in toes of diabetic patients independent of diabetes duration and macrocirculation. The aim of this study was to examine its relation to metabolic control. The skin microcirculation was investigated in 20 patients with insulin-dependent diabetes mellitus: 10 patients with bad [HbA1c > 7.5 (8.7 +/- 0.8) %], and 10 patients with good metabolic control [HbA1c < 7.5 (6.3 +/- 1.0) %]. The diabetes duration was similar in both groups (16 +/- 9 and 16 +/- 6 years, respectively). None had macroangiopathy. Thirteen healthy subjects served as controls. The capillary blood cell velocity (CBV) in the nailfold of the great toe was investigated by videophotometric capillaroscopy, and the total skin microcirculation by laser Doppler fluxmetry (LDF). CBV and LDF were studied during rest and after 1-min arterial occlusion. The vibration perception thresholds (VPT) of the feet were higher (p < 0.05) in the patients with bad (34 +/- 12 V), as compared to patients with good metabolic control (18 +/- 10 V) and to healthy subjects (13 +/- 3 V). Peak CBV during PRH was reduced in both patient groups (p < 0.01), and lowest in the patients with bad metabolic control (p < 0.05). Time to peak CBV was prolonged (p < 0.01) in the patients with bad, while normal in the patients with good metabolic control. LDF was similar in all groups. An inverse correlation was found between HbA1c and peak CBV during PRH (r = 0.60; p = 0.008), while positive correlations were found to time to peak CBV (r = 0.62; p = 0.004) and VPT (r = 0.60; p = 0.01). No associations were seen between VPT and the microcirculatory variables. The results indicate that the metabolic control is of importance for the nutritive capillary circulation and the peripheral nerve function in the diabetic foot.

Adult↗
PubMed1998

Fibroblasts derived from human chronic diabetic wounds have a decreased proliferation rate, which is recovered by the addition of heparin.

We have studied the growth kinetics of fibroblasts derived from uninjured skin and chronic wounds in non-diabetic and diabetic (IDDM) patients. DNA measurements during the first 24 h after cell starvation showed that fibroblasts derived from chronic wounds, both non-diabetic and diabetic, display a decreased adhesion and proliferation. When determining the rate of proliferation after another 48, 72 and 96 h, a significant decrease in the proliferation rate was found in the chronic wound fibroblasts compared to those from uninjured skin. Furthermore, we have investigated the effects of heparin, hyaluronic acid and other heparin-like substances on the proliferation of non-diabetic and diabetic fibroblasts. We found that these substances stimulated the proliferation of human fibroblasts derived from both normal skin and chronic wounds measured as DNA content. Stimulation with heparin normalized the proliferation of the diabetic chronic wound fibroblasts. This effect was independent of the presence of serum. The effect of heparin was dose-dependent and most pronounced during the first 24 h of stimulation. These results suggest that heparin may be of importance in the treatment of chronic diabetic wounds.

Anticoagulants↗
PubMed1998

Insulin-like growth factor-I and insulin-like growth factor binding protein-1 in a representative population of type 2 diabetic patients in Sweden.

OBJECTIVE: To study the influence of type 2 diabetes on the insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) serum levels in an area-based population of type 2 patients previously described. RESULTS: The patients (n = 151) were elderly (70.6 +/- 0.7 years of age) and moderately overweight (BMI 27.0 +/- 0.4 kg/m2). Most patients (83%) were treated with either diet alone or diet in combination with sulphonylurea. Metabolic control measured as HbAlc deteriorated with duration (p < 0.001) and between groups treated with diet (HbA1c 5.8 +/- 0.6), sulphonylurea (7.5 +/- 0.2) and insulin (7.7 +/- 0.4). Mean levels of IGF-I were within reported normal range, but were lower in the insulin-treated as compared to the non-insulin-treated patients. Levels of IGF-I decreased with diabetes duration and with increased blood glucose. There was a positive correlation between IGF-I and insulin levels and also an inverse correlation between IGF-I and IGFBP-1 levels. The IGFBP-1 levels were twofold higher than reported in non-diabetic individuals. In multiple stepwise correlation analysis, 37% of the variability in IGFBP-1 could be explained by BMI, IGF-I SD score, age, IGF-I, and fasting blood glucose. CONCLUSION: Our study indicates that influence of type 2 diabetes on IGF-I bioavailability in individual patients is modulated by insulin, body weight (presumably reflecting insulin sensitivity) and metabolic control. Furthermore, increased levels of IGFBP-1 are strongly associated with decreased b-cell function in type 2 diabetes mellitus.

Aged↗
PubMed1998

Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery.

Elective surgery was performed after overnight fasting, a routine that may affect the metabolic response to surgery. We investigated the effects of insulin and glucose infusions before and during surgery on postoperative substrate utilization and insulin sensitivity. Seven patients were given insulin and glucose infusions 3 h before and during surgery (insulin group), and a control group of six patients underwent surgery after fasting overnight. Insulin sensitivity and glucose kinetics (D-[6,6-2H2]glucose) were measured before and immediately after surgery using a hyperinsulinemic, normoglycemic clamp. Glucose infusion rates and whole body glucose disposal decreased after surgery in the control group (-40 and -29%, respectively), whereas no significant change was found in the insulin group (+16 and +25%). Endogenous glucose production remained unchanged in both groups. Postoperative changes in cortisol, glucagon, fat oxidation, and free fatty acids were attenuated in the insulin group (vs. control). We conclude that perioperative insulin and glucose infusions minimize the endocrine stress response and normalize postoperative insulin sensitivity and substrate utilization.

Arthroplasty, Replacement, Hip↗
PubMed1998

Insulin-like growth factor binding protein-1 as a marker of the metabolic syndrome--a study in borderline hypertension.

AIM: To evaluate insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) in borderline hypertension (BHT) in relation to plasma lipoprotein and insulin levels, anthropometric variables and 24-h ambulatory blood pressure (BP). Seventy-five BHT men diastolic BP (DBP) 85-94 mmHg) and 75 age-matched normotensive controls (NT, DBP < or = 80 mmHg) were recruited from a population-based screening program. RESULTS: There was no difference in IGF-I or IGFBP-1 between BHT and NT men. However, subjects with insulin resistance (IR) had decreased levels of IGF-1 (145 +/- 36 vs 153 +/- 28 microg/L, p < 0.05) and IGFBP-1 (41 +/- 15 vs 52 +/- 20 microg/L, p < 0.01) compared to those without IR. IGF-I correlated inversely to BP levels in the BHT group (r = -0.24 to -0.28, p < 0.05). IGFBP-1 correlated inversely with BMI, lipoprotein and insulin levels (r = -0.29 to -0.48, p < 0.01), independent of IR. CONCLUSION: While there are no differences between BHT and NT men in IGF-I and IGFBP-1, both are significantly decreased in IR subjects. IGFBP-1 exhibits a close correlation to metabolic factors. Decreased IGFBP-1 could thus be suggested as a variable marking the "metabolic syndrome" of hypertension.

Adult↗
PubMed1997

Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease.

The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor beta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-beta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 +/- 1 y (mean +/- SD), with a body mass index (BMI; in kg/m2) of 17.2 +/- 0.5 and various noncancer disorders, and 22 healthy matched control subjects aged 72 +/- 1 y, with a BMI of 25.4 +/- 0.7 (significantly different from patients, P < 0.001), were included. Fifteen patients and their corresponding control subjects were reexamined 3 mo later. Isolated monocytes were stimulated with lipopolysaccharide (LPS) and concentrations of IL-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrations of IL-6, IL-1ra, IL-10, TGF-beta 1, and acute-phase reactants were analyzed. Serum concentrations of orosomucoid and IL-6 were higher in the malnourished subjects than in the control subjects (1.14 +/- 0.1 compared with 0.8 +/- 0.3 g/L, P < 0.001; and 5 ng/L compared with undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1 beta (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was found in monocytes from patients with PEM relative to the control subjects when monocytes were stimulated with 0.1 microgram LPS/L. Monocyte TNF generation and serum concentrations of IL-10, IL-1ra, and TGF-beta 1 did not differ. Similar results were obtained at follow-up. IL-1ra was negatively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cytokines such as IL-6 and IL-1 beta in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.

Aged↗