STUDY OBJECTIVES:Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis.... Show moreSTUDY OBJECTIVES:Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis. Here, we evaluated whether human hypocretin deficiency, or the narcolepsy therapeutic agent sodium oxybate, alter the levels of these hormones. METHODS:Eight male, medication free, hypocretin deficient, narcolepsy with cataplexy patients, and 8 healthy controls matched for age, sex, body mass index (BMI), waisttohip ratio, and body fat percentage were assessed. Blood samples of total ghrelin and leptin were collected over 24 hours at 60 and 20-min intervals, respectively, during 2 study occasions: baseline, and during the last night of 5 consecutive nights of sodium oxybate administration (2 × 3.0 g/night). RESULTS:At baseline, mean 24-h total ghrelin (936 ± 142 vs. 949 ± 175 pg/mL, p = 0.873) and leptin (115 ± 5.0 vs. 79.0 ± 32 mg/L, p = 0.18) levels were not different between hypocretin deficient narcolepsy patients and controls. Furthermore, sodium oxybate did not significantly affect the plasma concentration of either one of these hormones. CONCLUSIONS:The increased BMI of narcolepsy patients is unlikely to be mediated by hypocretin deficiency-mediated alterations in total ghrelin or leptin levels. Thus, the effects of these hormones on hypocretin neurons may be mainly unidirectional. Although sodium oxybate may influence body weight, the underlying mechanism is unlikely to involve changes in total ghrelin or leptin secretion. Show less
Fronczek, R.; Geest, S. van; Frolich, M.; Overeem, S.; Roelandse, F.W.C.; Lammers, G.J.; Swaab, D.F. 2012
Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble... Show moreSleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. AD is a neurodegenerative disorder targeting different brain areas and types of neurons. In this study, we assessed whether the neurodegenerative process of AD also affects hypothalamic hypocretin/orexin neurons. The total number of hypocretin-1 immunoreactive neurons was quantified in postmortem hypothalami of AD patients (n = 10) and matched controls (n = 10). In addition, the hypocretin-1 concentration was measured in postmortem ventricular cerebrospinal fluid of 24 AD patients and 25 controls (including the patients and controls in which the hypothalamic cell counts were performed). The number of hypocretin-1 immunoreactive neurons was significantly decreased by 40% in AD patients (median [25th–75th percentiles]); AD 12,935 neurons (9972–19,051); controls 21,002 neurons (16,439–25,765); p = 0.049). Lower cerebrospinal fluid (CSF) hypocretin-1 levels were found in AD patients compared with controls (AD: 275 pg/mL [197–317]; controls: 320 pg/mL [262–363]; p = 0.038). Two AD patients with documented excessive daytime sleepiness showed the lowest CSF hypocretin-1 concentrations (55 pg/mL and 76 pg/mL). We conclude that the hypocretin system is affected in advanced AD. This is reflected in a 40% decreased cell number, and 14% lower CSF hypocretin-1 levels. Show less
Context: Reduction of 50% excess body weight, using a very low-calorie diet (VLCD; 450 kcal/d) improves insulin sensitivity in obese type 2 diabetes mellitus patients. Objective: The objective of... Show moreContext: Reduction of 50% excess body weight, using a very low-calorie diet (VLCD; 450 kcal/d) improves insulin sensitivity in obese type 2 diabetes mellitus patients. Objective: The objective of the study was to evaluate whether adding exercise to the VLCD has additional benefits. Design: This was a randomized intervention study. Setting: The study was conducted at a clinical research center in an academic medical center. Subjects: Twenty-seven obese [body mass index 37.2 ± 0.9 kg/m2 (mean ± sem)] insulin-treated type 2 diabetes mellitus patients. Intervention: Patients followed a 16-wk VLCD. Thirteen of them simultaneously participated in an exercise program (E) consisting of 1-h, in-hospital training and four 30-min training sessions on a cycloergometer weekly. Outcome Measures: Insulin resistance was measured by a hyperinsulinemic euglycemic clamp. Insulin signaling, mitochondrial DNA (mtDNA) content, and intramyocellular lipid content was measured in skeletal muscle biopsies. Results: Baseline characteristics were identical in both groups. Substantial by Browse to Save" href="http://jcem.endojournals.org/content/97/7/2512#" mce_href="http://jcem.endojournals.org/content/97/7/2512#">weight loss occurred (−23.7 ± 1.7 kg VLCD-only vs. −27.2 ± 1.9 kg VLCD+E, P = NS within groups). The exercise group lost more fat mass. Insulin-stimulated glucose disposal increased similarly in both study groups [15.0 ± 0.9 to 39.2 ± 4.7 μmol/min−1 · kg lean body mass (LBM−1) VLCD-only vs. 17.0 ± 1.0 to 37.5 ± 3.5 μmol/min−1 · kg LBM−1 in VLCD+E], as did phosphorylation of the phosphatidylinositol 3-kinase-protein kinase B/AKT insulin signaling pathway. In contrast, skeletal muscle mtDNA content increased only in the VLCD+E group (1211 ± 185 to 2288 ± 358, arbitrary units, P = 0.016 vs. 1397 ± 240 to 1196 ± 179, P = NS, VLCD-only group). Maximum aerobic capacity also only increased significantly in the VLCD+E group (+6.6 ± 1.7 ml/min−1 · kg LBM−1 vs. +0.7 ± 1.5 ml/min−1 · kg LBM−1 VLCD-only, P = 0.017). Conclusion: Addition of exercise to a 16-wk VLCD induces more fat loss. Exercise augments maximum aerobic capacity and skeletal muscle mtDNA content. These changes are, however, not reflected in a higher insulin-stimulated glucose disposal rate. Show less
Rozing, M.P.; Westendorp, R.G.J.; Maier, A.B.; Wijsman, C.A.; Frolich, M.; Craen, A.J.M. de; Heemst, D. van 2012
Increasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to... Show moreIncreasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to enhance production of inflammatory cytokines. In view of these considerations, we hypothesized a mutual association between triiodothyronine and pro-inflammatory cytokines. Therefore we evaluated the relation between both circulating and induced inflammatory markers and serum thyroid function parameters in the Leiden 85-plus Study. We found that higher circulating levels of inflammatory markers were associated with lower levels of free serum triiodothyronine. In turn, higher serum free triiodothyronine levels were related to higher production capacity of pro-inflammatory cytokines after stimulation with lipopolysaccharide. By combining in vivo and ex vivo data, we were able to demonstrate for the first time the existence of a potential feedback mechanism between thyroid function and immune production capacity. We conclude that maintenance of normal thyroid function might be important for a preserved immune response in elderly human populations. Show less
Freeman, D.J.; Robertson, M.; Brown, E.A.; Rumley, A.; Tobias, E.S.; Frolich, M.; ... ; Stott, D.J. 2011
BACKGROUND Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE... Show moreBACKGROUND Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables. METHODS This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available. RESULTS There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE. CONCLUSIONS Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk. TRIAL REGISTRATION Not applicable when study undertaken. Show less
Freeman, D.J.; Robertson, M.; Brown, E.A.; Rumley, A.; Tobias, E.S.; Frolich, M.; ... ; Stott, D.J. 2011
Increasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to... Show moreIncreasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to enhance production of inflammatory cytokines. In view of these considerations, we hypothesized a mutual association between triiodothyronine and pro-inflammatory cytokines. Therefore we evaluated the relation between both circulating and induced inflammatory markers and serum thyroid function parameters in the Leiden 85-plus Study. We found that higher circulating levels of inflammatory markers were associated with lower levels of free serum triiodothyronine. In turn, higher serum free triiodothyronine levels were related to higher production capacity of pro-inflammatory cytokines after stimulation with lipopolysaccharide. By combining in vivo and ex vivo data, we were able to demonstrate for the first time the existence of a potential feedback mechanism between thyroid function and immune production capacity. We conclude that maintenance of normal thyroid function might be important for a preserved immune response in elderly human populations. Show less
Rozing, M.P.; Houwing-Duistermaat, J.J.; Slagboom, P.E.; Beekman, M.; Frolich, M.; Craen, A.J.M. de; ... ; Heemst, D. van 2010
Context: A relation between low thyroid activity and prolonged life span in humans has been observed. Several studies have demonstrated hereditary and genetic influences on thyroid function.... Show moreContext: A relation between low thyroid activity and prolonged life span in humans has been observed. Several studies have demonstrated hereditary and genetic influences on thyroid function. Objective: The objective of the study was to test whether low thyroid activity associated with extreme longevity constitutes a heritable phenotype, which could contribute to the familial longevity observed in the Leiden Longevity Study. Design: This was a cross-sectional study. Setting: The study was conducted at a university hospital in the city of Leiden, The Netherlands. Participants: Eight hundred fifty-nine nonagenarian siblings (median age 92.9 yr) from 421 long-lived families participated in the study. Families were recruited from the entire Dutch population if at least two long-lived siblings were alive and fulfilled the age criterion of age of 89 yr or older for males and 91 yr or older for females. There were no selection criteria on health or demographic characteristics. Intervention: Blood samples were taken for determination of serum parameters of thyroid function. Main Outcome Measure: We calculated the family mortality history score of the parents of the nonagenarian siblings and related this to thyroid function parameters in the nonagenarian siblings. Results: We found that a lower family mortality history score (less mortality) of the parents of nonagenarian siblings was associated with higher serum TSH levels (P = 0.005) and lower free T-4 levels (P = 0.002) as well as lower free T-3 levels (P = 0.034) in the nonagenarian siblings. Conclusions: Our findings support the previous observation that low thyroid activity in humans constitutes a heritable phenotype that contributes to exceptional familial longevity observed in the Leiden Longevity Study. (J Clin Endocrinol Metab 95: 4979-4984, 2010) Show less
Aziz, N.A.; Pijl, H.; Frolich, M.; Snel, M.; Streefland, T.C.M.; Roelfsema, F.; Roos, R.A.C. 2010
Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the HTT gene. Apart from neurological impairment, the disease is also... Show moreBackground Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the HTT gene. Apart from neurological impairment, the disease is also accompanied by progressive weight loss, abnormalities in fat and glucose homeostasis and a higher prevalence of diabetes mellitus, the causes of which are unknown. Therefore, a detailed analysis of systemic energy homeostasis in HD patients in relation to disease characteristics was performed. Methods Indirect calorimetry combined with a hyperinsulinaemic-euglycaemic clamp with stable isotopes ([6,6-2H2]-glucose and [2H5]- glycerol) was performed to assess energy expenditure and glucose and fat metabolism in nine early stage, medication free HD patients and nine age, sex and body mass index matched controls. Results Compared with controls, fasting energy expenditure was higher in HD patients (1616 +/- 72 vs 1883 +/- 93 kcal/24 h, p=0.037) and increased even further after insulin stimulation (1667 +/- 87 vs 2068 +/- 122 kcal/24 h, p=0.016). During both basal and hyperinsulinaemic conditions, glucose and glycerol disposal rates, endogenous glucose production and hepatic insulin sensitivity were similar between HD patients and controls. In HD patients, energy expenditure increased with disease duration but not with a greater degree of motor or functional impairment. Moreover, a higher mutant CAG repeat size was associated with lower insulin sensitivity (r=-0.84, p=0.018). Conclusion These findings suggest sympathetic hyperactivity as an underlying mechanism of increased energy expenditure in HD, as well as peripheral polyglutamine length dependent interference of mutant huntingtin with insulin signalling that may become clinically relevant in carriers of mutations with large CAG repeat sizes. Show less
P>Background Recently, a loss of hypothalamic dopamine D-2 receptors was demonstrated in Huntington's disease (HD). Activation of dopamine D-2 receptors is known to inhibit the function of both... Show moreP>Background Recently, a loss of hypothalamic dopamine D-2 receptors was demonstrated in Huntington's disease (HD). Activation of dopamine D-2 receptors is known to inhibit the function of both thyrotropic and lactotropic axes. Objective To assess whether the activity of the thyrotropic and lactotropic axes is disturbed in patients with HD, contributing to symptoms such as unintended weight loss. Participants and methods In nine medication-free patients with early-stage HD (six men, three women) and nine age-, sex- and body mass index-matched controls, we measured serum levels of thyroid-stimulating hormone (TSH) and prolactin (men only) every 10 min for 24 h. Multiparameter auto-deconvolution and approximate entropy analysis were applied to quantify basal, pulsatile and total TSH and prolactin secretion rates as well as the regularity of hormone release. Results Compared with controls, TSH and prolactin secretion tended to be slightly, but not significantly, higher in patients with HD (TSH: 1 center dot 13 +/- 0 center dot 14 vs 0 center dot 91 +/- 0 center dot 19 mU/l, P = 0 center dot 40; prolactin: 213 +/- 18 vs 209 +/- 11 pmol/l, P = 0 center dot 87). However, in patients with HD, total T-3 levels were significantly higher (1 center dot 60 +/- 0 center dot 05 vs 1 center dot 35 +/- 0 center dot 09, P = 0 center dot 045), while T-4 levels tended to be higher as well (91 center dot 9 +/- 3 center dot 9 vs 81 center dot 3 +/- 3 center dot 1, P = 0 center dot 085). Prolactin secretion was significantly more irregular in patients with HD (Approximate entropy (ApEn): 1 center dot 06 +/- 0 center dot 08 vs 0 center dot 80 +/- 0 center dot 09, P = 0 center dot 037). Total T-3 levels were negatively associated with motor impairment (r = -0 center dot 72, P = 0 center dot 030), whereas increasing free T-4 levels were associated with a larger mutant cytosine-adenine-guanine (CAG) repeat size (r = +0 center dot 68, P = 0 center dot 044). Conclusion: Our findings indicate a mild hyperactivity of the thyrotropic axis and a disturbed regulation of the lactotropic axis in patients with early-stage HD. Show less
Vidarsdottir, S.; Vlug, P.; Roelfsema, F.; Frolich, M.; Pijl, H. 2010
Objective: Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than... Show moreObjective: Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Method: Twelve healthy men (mean +/- SEM age: 25.1 +/- 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Results: Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Conclusions: Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. Trial Registration: controlled-trials.com. Identifier: ISRCTN17632637 J Clin Psychiatry 2010;71(9):1205-1211 (C) Copyright 2010 Physicians Postgraduate Press, Inc. Show less
Aziz, N.A.; Pijl, H.; Frolich, M.; Graaf, W.M. van der; Roelfsema, F.; Roos, R.A.C. 2010
P>Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss,... Show moreP>Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. Objective To perform a detailed analysis of adipose tissue function in HD patients as abnormal fat tissue function could contribute to the weight loss. Design, setting and participants In a clinical research laboratory, 24-h plasma concentrations of leptin, adiponectin and resistin were studied in nine early-stage, medication-free HD patients and nine age-, gender- and body mass index (BMI)-matched controls. Measurements Leptin was measured every 20 min whereas adiponectin and resistin were measured hourly. Autodeconvolution and cosinor regression were applied to quantify secretion characteristics of leptin and diurnal variations in leptin, adiponectin and resistin levels. Results Plasma levels and diurnal rhythmicity of leptin, adiponectin and resistin were not significantly different between HD patients and controls. However, although leptin production increased with higher BMI and fat mass in controls, no such relation was present in HD patients. Moreover, when corrected for fat mass, mean plasma leptin concentration as well as basal, pulsatile and total secretion rates increased with the size of the CAG repeat mutation (r = +0 center dot 72 to r = +0 center dot 80; all P < 0 center dot 05). Both higher pulsatile leptin secretion and higher mean adiponectin levels were associated with a greater degree of motor and functional impairment in HD patients. Conclusions CAG-repeat size-dependent interference of the HD mutation with adipose tissue function may contribute to weight loss in HD patients. Show less
Goekoop, R.J.; Kloppenburg, M.; Kroon, H.M.; Frolich, M.; Huizinga, T.W.J.; Westendorp, R.G.J.; Gussekloo, J. 2010
Objective: We investigated whether innate differences in cytokine response were associated with the absence of osteoarthritis (OA) in old age. Design: In 82 participants from a cross-sectional... Show moreObjective: We investigated whether innate differences in cytokine response were associated with the absence of osteoarthritis (OA) in old age. Design: In 82 participants from a cross-sectional birth cohort, radiographs of hands, hips and knees were taken at the age of 90 years. OA was defined as a Kellgren-Lawrence score of at least two. "Free from OA" was defined at patient level as absence of hip and knee OA, and presence of OA in maximally two hand joints. The innate cytokine response was determined in whole-blood samples upon stimulation with lipopolysaccharide. Logistic regression analyses were used to investigate associations between absence of OA in relation to tertiles of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-1 receptor antagonist (RA) and IL-10. Adjustments were made for gender and body mass index. Results: Sixteen percent of the participants were "free from OA". Subjects in the lowest tertile of II-1 beta production had a 11-fold increased chance to be free of OA [odds ratio (OR) 11.3, confidence intervals (CI) 95% 1.1-115.9], subjects in the lowest tertile of IL-6 production had an almost 7-fold increased chance to be free of OA (OR 6.7, 95% CI 1.1-41.2). Absence of hand OA was associated with low innate production of IL-6 and IL-1RA, absence of hip OA was associated with low innate IL-1 beta production. No associations were found for TNF-alpha and IL-10. Conclusions: Low innate capacity to produce the pro-inflammatory cytokines IL-1 beta and IL-6 is associated with the absence of OA in old age. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Goekoop, R.J.; Kloppenburg, M.; Kroon, H.M.; Frolich, M.; Huizinga, T.W.J.; Westendorp, R.G.J.; Gussekloo, J. 2010
OBJECTIVE We investigated whether innate differences in cytokine response were associated with the absence of osteoarthritis (OA) in old age. DESIGN In 82 participants from a cross-sectional birth... Show moreOBJECTIVE We investigated whether innate differences in cytokine response were associated with the absence of osteoarthritis (OA) in old age. DESIGN In 82 participants from a cross-sectional birth cohort, radiographs of hands, hips and knees were taken at the age of 90 years. OA was defined as a Kellgren-Lawrence score of at least two. "Free from OA" was defined at patient level as absence of hip and knee OA, and presence of OA in maximally two hand joints. The innate cytokine response was determined in whole-blood samples upon stimulation with lipopolysaccharide. Logistic regression analyses were used to investigate associations between absence of OA in relation to tertiles of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-1 receptor antagonist (RA) and IL-10. Adjustments were made for gender and body mass index. RESULTS Sixteen percent of the participants were "free from OA". Subjects in the lowest tertile of Il-1beta production had a 11-fold increased chance to be free of OA [odds ratio (OR) 11.3, confidence intervals (CI) 95% 1.1-115.9], subjects in the lowest tertile of IL-6 production had an almost 7-fold increased chance to be free of OA (OR 6.7, 95% CI 1.1-41.2). Absence of hand OA was associated with low innate production of IL-6 and IL-1RA, absence of hip OA was associated with low innate IL-1beta production. No associations were found for TNF-alpha and IL-10. CONCLUSIONS Low innate capacity to produce the pro-inflammatory cytokines IL-1beta and IL-6 is associated with the absence of OA in old age. Show less
