Urinary IL-6 Levels Research Articles

Short-Term Treatment of Recombinant Murine Interleukin-4 Rapidly Inhibits Bone Formation in Normal and Ovariectomized Mice

Estrogen deficiency contributes to an increase in bone resorption and bone formation characterized by a high rate of bone turnover. Interleukin-4 (IL-4) is a rapid and potent inhibitor of bone resorption. We examined the short term in vivo effects of recombinant murine IL-4 (rmIL-4) on bone remodeling in normal and ovariectomized mice. Eight-week-old mice were randomized into the following five groups: (1) sham-operated mice (sham); (2) sham-operated mice infused with rmIL-4; (3) ovariectomized mice (ovx); (4) ovx infused with rmIL-4; and (5) ovx replaced by 10 or 20 μg of 17β-estradiol (E 2) for 14 or 28 days after ovariectomy, respectively. rmIL-4 at a dose of 5 μg/day was infused into ovx and sham for 3 days prior to sacrifice. Analyses were performed 14 and 28 days after operation. An increase in serum alkaline phosphatase and urinary deoxypyridinoline levels induced by ovariectomy was inhibited by the 3-day infusion of rmIL-4. In ovx, serum and urinary IL-6 levels were also increased significantly 14 days after ovariectomy, which were restored by E 2 but not by rmIL-4. Histomorphometrical analysis of trabecular bone revealed that the 3-day infusion of rmIL-4 inhibited the high rate of bone turnover induced by ovariectomy, such as an increase in the osteoclastic surface (Oc.S/BS), number of osteoclasts per mm bone surface (N.Oc/BS), mineralized surface per mm bone surface (MS/BS), and bone mineral apposition rate (MAR). A significant decrease in the bone volume (BV/TV) observed in ovx was not modulated by a 3-day infusion of rmIL-4 prior to sacrifice. In sham, rmIL-4 also caused a significant decrease in the Oc.S/BS, N.Oc/BS, MS/BS, and MAR, but the BV/TV was not modulated by rmIL-4. We conclude that short term infusion of rmIL-4 in vivo rapidly inhibits not only bone resorption but also its formation in both sham-operated and ovariectomized growing mice, resulting in a low rate of bone turnover without modulating bone volume.

Sequential monitoring of urine-soluble interleukin 2 receptor and interleukin 6 predicts acute rejection of human renal allografts before clinical or laboratory signs of renal dysfunction.

The significance of noninvasive techniques to the early diagnosis of acute rejection in kidney transplants remains elusive. In this study, we examined whether an early posttransplant increase in serum- and urine-soluble interleukin (IL) 2 receptor (sIL-2R) and IL-6 levels predicted acute rejection. Sequential determinations of serum and urine sIL-2R and IL-6 were performed in the first 30 postoperative days in 40 renal transplant patients. Changes during the posttransplant period observed in 26 patients who had one or more episodes of acute rejection (group A) were compared with those recorded in 14 patients who did not experience acute rejection of their graft (group B). Serum sIL-2R was higher than normal in patients of groups A and B without statistical differences between the two groups. In the first 3 days after transplantation, urinary sIL-2R was higher than normal in group A but not in group B. Urinary sIL-2R at days 2 and 3 was significantly higher (P<0.05) in group A than in group B. In the first 5 days after transplantation, urinary IL-6 was persistently higher than normal in group A, whereas it progressively decreased to normal value on day 4 in group B. Sudden increases (doubling within 24 hr) in urine IL-6 preceded clinical diagnosis of acute rejection by a mean period of 2 days, with an 87% sensitivity and a 64% specificity, and also predicted recurrent rejection episodes. Sequential monitoring of urinary sIL-2R and IL-6 levels does allow very early diagnosis of rejection without invasive procedures. Specifically, high urinary sIL-2R in the first 5 posttransplant days identifies the subgroup of patients at risk. In the subsequent days, a sudden increase in urinary IL-6 occurs in those of the above patients who will indeed reject their graft.

Known bacterial virulence factors do not explain the variation in urinary cytokine levels in patients with urosepsis

We measured urinary endotoxin, IL-6 and IL-8 levels in 23 patients with gram-negative urosepsis. The endotoxin and cytokine levels showed a 100–1000 fold range. No correlation was found between levels of urinary endotoxin, and IL-6 or IL-8 levels. In all cases bacterial numbers were ≥ 10 5 CFU ml −1 urine. The endotoxin content of the isolated microorganisms neither correlated with the urinary cytokine levels, nor with IL-6 and IL-8 levels obtained in vitro when 10 3 log-phase CFU of each of the bacteria were incubated with heparinized whole blood of three healthy donors. Neither the haemolysin phenotype of the bacteria, nor the presence of the P-pili gene was correlated with the cytokine response in vivo or in vitro. Other factors than known bacterial virulence factors apparently contribute to the wide variation in urinary cytokine levels in urinary tract infection.

Known bacterial virulence factors do not explain the variation in urinary cytokine levels in patients with urosepsis.

We measured urinary endotoxin, IL-6 and IL-8 levels in 23 patients with gram-negative urosepsis. The endotoxin and cytokine levels showed a 100-1000 fold range. No correlation was found between levels of urinary endotoxin, and IL-6 or IL-8 levels. In all cases bacterial numbers were > or = 10(5) CFU ml-1 urine. The endotoxin content of the isolated microorganisms neither correlated with the urinary cytokine levels, nor with IL-6 and IL-8 levels obtained in vitro when 10(3) log-phase CFU of each of the bacteria were incubated with heparinized whole blood of three healthy donors. Neither the haemolysin phenotype of the bacteria, nor the presence of the P-pili gene was correlated with the cytokine response in vivo or in vitro. Other factors than known bacterial virulence factors apparently contribute to the wide variation in urinary cytokine levels in urinary tract infection.

Interleukin-8 and the neutrophil response to mucosal gram-negative infection.

Urinary tract infections activate a mucosal inflammatory response, which includes cytokine secretion and neutrophil influx. The mechanisms involved in the neutrophil influx have not been identified. Interleukin-8, a potent chemoattractant for neutrophils, is produced by urinary tract epithelial cell lines in vitro. This study analyzed the human IL-8 response to deliberate Escherichia coli infection of the urinary tract. Urine and serum samples were obtained before and after intravesical instillation of E. coli. Neutrophil numbers were determined on uncentrifuged urine, and IL-8 levels were measured by ELISA. A urinary IL-8 response was found in all patients after bacterial instillation, but no serum IL-8 was detected. There was a strong correlation between urinary IL-8 levels and urinary neutrophil numbers. The same E. coli strains used to colonize the patients stimulated IL-8 production in urinary tract epithelial cells. The level of IL-8 secreted by epithelial cell lines was influenced by the fimbrial properties of the E. coli. These results demonstrated that E. coli elicit a mucosal IL-8 response in humans, and suggested that IL-8 is involved in the onset of pyuria. Epithelial cells may be an important source of IL-8 during urinary tract infection.

抽出法およびＥＬＩＳＡ法を組み合わせた尿中ＩＬ‐６測定系の検討とメサンギウム増殖性腎炎患者における尿中ＩＬ‐６濃度の臨床的意義

The simple extraction technique of urinary IL-6 was developed, so urinary IL-6 levels can be measured by enzyme linked immunosorbent assay (ELISA) method without the influences of non-specific reactions and/or inhibitors. The urinary IL-6 levels in active stage of MesPGN cases were higher than those of remission stage of MesPGN cases, healthy cases and other glomerular disease cases. And in remission stage of MesPGN cases, urinary IL-6 levels were same level as in healthy cases.These data suggest that measurement of levels of urinary IL-6 is helpful for the diagnosis and evaluation of clinical activities of MesPGN.