Usefulness of a Highly Sensitive Urinary and Serum IL-6 Assay in Patients with Diabetic Nephropathy

Shikano, Masahiko; Sano, Hiroshi; Yoshikawa, Hiroto; Toba, Takako; Kushimoto, Hiroko; Katsumata, Hideki; Tomita, Makoto; Kawashima, Shirou

doi:10.1159/000045634

Cited by 111 publications

(73 citation statements)

References 14 publications

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“…18 There is also evidence that IL-6 production by human monocytes isolated from healthy volunteers is enhanced during 24-hour incubation in high-glucose medium. 19 Previous studies have demonstrated increased circulating levels of TNF-␣ and IL-6 in diabetic patients, 3,5-8 with a significant correlation of IL-6 levels with HbA 1 c, 7 progression of diabetic nephropathy, 8 and amelioration of glycemic control after treatment. 6 In a more general sense, an augmented acute-phase response may be a mechanism that explains many of the clinical and biochemical features of type 2 diabetes and its complications.…”

Section: Discussionmentioning

confidence: 98%

“…4 Moreover, several studies have demonstrated elevated levels of IL-6 and tumor necrosis factor-␣ (TNF-␣) among individuals both with features of the insulin resistance syndrome and with clinically overt type 2 diabetes mellitus. [5][6][7][8] The aim of the present study was to test whether circulating levels of cytokines are regulated by glucose levels in humans. The study protocol was designed to measure serum TNF-␣, IL-6 and interleukin-18 (IL-18) concentrations during acute hyperglycemia in subjects with normal or impaired glucose tolerance (IGT); a role for IL-18 in plaque destabilization has recently been suggested, 9 and stress hyperglycemia is an important risk factor for post-myocardial infarction mortality in subjects with or without diabetes.…”

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confidence: 99%

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Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

et al. 2002

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Background-Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-␣ (TNF-␣) are elevated in diabetic patients. We assessed the role of glucose in the regulation of circulating levels of IL-6, TNF-␣, and interleukin-18 (IL-18) in subjects with normal or impaired glucose tolerance (IGT), as well as the effect of the antioxidant glutathione. Methods and Results-Plasma glucose levels were acutely raised in 20 control and 15 IGT subjects and maintained at 15 mmol/L for 5 hours while endogenous insulin secretion was blocked with octreotide. In control subjects, plasma IL-6, TNF-␣, and IL-18 levels rose (PϽ0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In another study, the same subjects received 3 consecutive pulses of intravenous glucose (0.33 g/kg) separated by a 2-hour interval. Plasma cytokine levels obtained at 3, 4, and 5 hours were higher (PϽ0.05) than the corresponding values obtained during the clamp. The IGT subjects had fasting plasma IL-6 and TNF-␣ levels higher (PϽ0.05) than those of control subjects. The increase in plasma cytokine levels during the clamping lasted longer (4 hours versus 2 hours, PϽ0.01) in the IGT subjects than in the control subjects, and the cytokine peaks of IGT subjects after the first glucose pulse were higher (PϽ0.05) than those of control subjects. On another occasion, 10 control and 8 IGT subjects received the same glucose pulses as above during an infusion of glutathione; plasma cytokine levels did not show any significant change from baseline after the 3 glucose pulses. Conclusions-Hyperglycemia acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with IGT. This suggests a causal role for hyperglycemia in the immune activation of diabetes.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

et al. 2002

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“…25 The intra-day and inter-day coefficients of variation (CV) of this assay were 1.5-5.5% and 3.3-4.5%, respectively. This assay format is based on the two-step sandwich CL-EIA method as follows: aliquots 50 µL of each sample were added to 250µ L of suspension of ferrite microparticles coated with a monoclonal antibody against IL-6 as a solid phase and There were no significant differences in IL-6 concentrations (period 1) between the smokers and non-smokers (p=0.48) or between patients with and without periodontal disease (p=0.37).…”

Section: Stimulated Saliva Sample Preparationmentioning

confidence: 88%

Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma

Sato¹,

Goto²,

Murata³

et al. 2010

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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Objective: To elucidate the changes in interleukin-6 (IL-6) levels in whole saliva during the treatment phase in patients with oral squamous cell carcinoma (OSCC).Study Design: Twenty-nine consecutive inpatients with OSCC were enrolled in this study. Stimulated saliva was collected three times (just after hospitalization)[period 1], just before main treatment (surgery: 26/29 cases)[period 2] and at the time of discharge [period 3]. The mean intervals were 11±8 days between periods 1 and 2 and 30±18 days between periods 2 and 3. As controls, 19 age-matched healthy volunteers were also recruited. IL-6 concentrations were measured by a highly sensitive chemiluminescent enzyme immunoassay.

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“…Expression studies have also shown IL-6 mRNA in the mesangium of renal specimens from diabetic subjects [10]. IL-6 has in fact been shown to be the main stimulus for the hepatic production of CRP, and its gene transcripts are expressed in human atheromatous lesions.…”

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confidence: 98%

Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients

et al. 2003

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Aims/hypothesis. Increased concentrations of C-reactive protein and interleukin-6, a finding suggestive of the presence of inflammation, have been observed in Type 2 diabetes. In such patients, C-reactive protein was predictive of diabetic nephropathy. Studies on low-grade inflammatory markers and nephropathy in Type 1 diabetic patients have shown conflicting results. Therefore we studied whether low-grade inflammation is associated with diabetic nephropathy in Type 1 diabetic patients. Methods. We divided 194 Type 1 diabetic patients into three groups from the Finnish Diabetic Nephropathy Study based upon their albumin excretion rate. Patients with normoalbuminuria (n=67) had no antihypertensive medication or signs of cardiovascular disease, while patients with microalbuminuria (n=64) or macroalbuminuria (n=63) were all treated with an angiotensin-converting enzyme inhibitor, a drug that could attenuate low-grade inflammation. As a measure of insulin sensitivity we used estimated glucose disposal rate. C-reactive protein was measured by radioimmunoassay and interleukin-6 by high sensitivity enzyme immunoassay.

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Usefulness of a Highly Sensitive Urinary and Serum IL-6 Assay in Patients with Diabetic Nephropathy

Cited by 111 publications

References 14 publications

Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma

Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients

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