Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.
Cytokines ; Homeostasis ; Interferons ; Interleukin-1 ; Interleukin-10 ; Interleukin-11 ; Interleukin-12 ; Interleukin-15 ; Interleukin-17 ; Interleukin-23 ; Interleukin-27 ; Interleukin-3 ; Interleukin-33 ; Interleukin-4 ; Interleukin-6 ; Interleukin-7 ; Interleukin-8 ; Macrophage Colony-Stimulating Factor ; Necrosis ; Osteoblasts ; Osteoclasts ; RANK Ligand

The present study was carried out in order to investigate the relationship between immune function and the activity of hypothalamic-pituitary-adrenal(HPA) axis in patients with major depression. The subjects were 16 female major depressives and 16 female healthy controls. We measured mitogen-induced production of IL-1 beta, IL-2, IL-6 and serum level of IL-1 beta, IL-2, IL-6 and basal plasma cortisol levels at 8 00 a.m. We measured post-DST(dexamethasone suppression test) cortisol levels in 16 major depressives. The result were as follows : 1) Basal cortisol level was significantly higher in the patients with major depression than in the healthy controls(14.4+/-4.6 microgram/dl, 10.1+/-5.2microgram /dl, respectively, p<0.05). 2) IL-2 production was significantly lower in the patients with major depression than in the healthy controls(1747.3+/-387.9 pg/ml, 2520.2+/-884.1 pg/ml, respectively, p<0.05). There were no significant differences in IL-1 beta and IL-6 production between the patients with major depression and the healthy controls. 3) Serum level of IL-2 was detectable in 12 of 16 patients with major depression and in 10 of 16 healthy controls. There was no significant difference in serum level of IL-2 between two groups. Serum level of IL-1 beta was detectable in 3 of 16 patients with major depression and of 16 healthy controls. We could not detect serum level of IL-6 in both groups. 4) There was significant negative correlation between IL-2 production and post-DST cortisol level(r= -0.89) in the 16 patients with major depression. There was significant negative correlation between serum level of IL-2 and post-DST cortisol level(r= -0.97) in the 12 patients with major depression. There was significant negative correlation between serum level of IL-2 and basal cortisol level(r= -0.65) in the 12 patients with major depression. But there was no significant correlation between IL-2 production and basal cortisol level in the 16 patients with major depression. These findings suggest that immune function is decreased in major depression and the decreased immune function is highly related to the hyperactivity of the HPA axis.
Axis, Cervical Vertebra* ; Depression* ; Female ; Humans ; Hydrocortisone ; Interleukin-1* ; Interleukin-1beta* ; Interleukin-2 ; Interleukin-6 ; Interleukins ; Plasma

PURPOSE: This study was undertaken to examine whether differences exist in the hemoglobin variability according to the types of erythropoiesis stimulating agent (ESA) in hemodialysis (HD) patients. METHODS: Clinical data were retrospectively analyzed from 72 patients on maintenance hemodialysis who were using darbepoetin alfa (n=27), epoetin beta (n=27), and epoetin alpha (n=18). As parameters of hemoglobin variability, hemoglobin cycling, the variance of hemoglobin and the SD/mean of hemoglobin were analyzed. Hemoglobin cycling was defined as the presence of cycles with an amplitude >1.5 g/dL and lasting more than 2 months. RESULTS: Hemoglobin cycling was present in 53 (73.6%) out of 72 HD patients. Hemoglobin cycling in patients receiving darbepoetin alfa had greater frequency (1.63+/-0.93 vs. 1.00+/-0.88 times/year, p<0.05), amplitude (2.88+/-1.48 vs. 1.88+/-1.60 g/dL, p<0.05), and velocity (1.21+/-0.74 vs. 0.73+/-0.66 g/dL/month, p<0.05) than that in patients receiving epoetin beta. The variance of hemoglobin in patients receiving epoetin beta (0.79+/-0.53 g/dL) was smaller than that in patients receiving darbepoetin alfa (1.29+/-0.70 g/dL, p<0.05) and epoetin alfa (1.08+/-0.52 g/dL, p<0.05). Also, the ratio of SD/mean of hemoglobin in patients receiving epoetin beta (8.20+/-2.59%) was lower than that in patients receiving darbepoetin alfa (10.81+/-2.10%, p<0.05) and epoetin alfa (10.30+/-2.10%, p<0.05). CONCLUSION: Hemoglobin variability is differential according to various ESAs, and it may be less with epoetin beta compared with darbepoetin alpha and epoetin alpha.
Anemia ; Erythropoiesis ; Erythropoietin ; Hematinics ; Hemoglobins ; Humans ; Recombinant Proteins ; Renal Dialysis ; Retrospective Studies ; Darbepoetin alfa ; Epoetin Alfa

PURPOSE: We aim to compare the erythropoietic effects of epoetin-alpha (EA, 4000 IU SC thrice a week) with those of darbepoetin-alpha (DA, 60ug IV weekly, conversion rate to EA=200:1). METHODS: Forty one stable hemodialysis patients were enrolled in this randomized crossover study. After a washout period of erythropoietin stimulating agents (ESA), the patients with hemoglobin (Hb) level of < or =11.0 g/dL were randomly assigned to DA or EA and we measured Hb and reticulocyte levels. When Hb reached >11.0 g/dL, we stopped ESA. When Hb level decreased to < or =11.0 g/dL again, we switched to alternative ESA and repeated the rest of the steps. RESULTS: Thirty six patients (M:F=20:16, age 62+/-11 years, Kt/V 1.65, nPCR 1.13 g/kg/day) completed the study. No significant differences were observed in baseline parameters between DA and EA during the period of the clinical trial. The rate of Hb level increase (EA 0.29 g/dL/week, DA 0.30 g/dL/week, p=0.76) and decrease (EA 0.45 g/dL/week, DA 0.38 g/dL/week, p=0.14) were not different between two periods. After ESA stopped, the duration of decreased Hb level of < or =11.0 g/dL was not significantly different (4 weeks in EA vs. 3.9 weeks in DA, p=0.86). Erythropoietin resistance index was 10.59 in the EA period. It was not significantly different from 10.97 in DA period (p=0.49). Nine patients (25%) showed a >30% change in EA efficiency relative to DA efficiency. CONCLUSION: There was no significant difference in erythropoietic parameters for both EA and DA.
Anemia ; Cross-Over Studies ; Erythropoietin ; Hemoglobins ; Humans ; Recombinant Proteins ; Renal Dialysis ; Reticulocytes ; Darbepoetin alfa ; Epoetin Alfa

BACKGROUND AND OBJECTIVES: The nasal epithelium is the first barrier encountered by airborne allergens and is an active participant in airway inflammation. The aim of this study was to determine the activation mechanism of nasal epithelial cells with Alternaria and the effect of rhinovirus on the Alternaria induced activation of nasal epithelial cells. MATERIALS AND METHODS: Cultured epithelial cells were stimulated by Alternaria with or without rhinovirus-16 (RV-16) infection. Release of interleukin (IL)-6, IL-8, and granulocyte macrophage colony-stimulating factor (GM-CSF) into culture supernatants were measured to determine the activation of epithelial cells. Nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) of the epithelial cells were analyzed using western blot analysis. Intracellular NF-kappaB and AP-1 activity were evaluated by enzyme-linked immunosorbent assay. To determine the epithelial cell activation mechanism, cytokine production was inhibited with NF-kB, AP-1, and mitogen activated protein kinase (MAPK) inhibitors. RESULTS: Exposure of epithelial cells to Alternaria enhanced the production of cytokines. Intracellular NF-kB expression and activity were significantly increased by Alternaria, but not by RV-16. AP-1 expression and activity were not influenced by Alternaria. Increased IL-6 production was significantly inhibited by transcription factor inhibitors. However, IL-8 and GM-CSF production were not inhibited by these transcription factor inhibitors. CONCLUSIONS: Our in-vitro results demonstrate that Alternaria activates nasal polyp epithelial cells via NF-kB pathway and that NF-kB, AP-1, and MAPK are involved in the production of IL-6.
Allergens ; Alternaria ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Granulocytes ; Inflammation ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Macrophage Colony-Stimulating Factor ; Nasal Mucosa ; Nasal Polyps ; NF-kappa B ; Protein Kinases ; Rhinovirus ; Transcription Factor AP-1 ; Transcription Factors

BACKGROUND: The phenotypic heterogeneity of psoriasis could be explained by the alternate activation of either T-helper (Th)-1- or Th-17-related cytokines. However, evidence directly supporting this hypothesis is scarce. OBJECTIVE: To characterize the expression of Th-1- and Th-17-related cytokines according to the morphological psoriasis phenotype: guttate vs. plaque. METHODS: In this study, we enrolled 68 patients exhibiting either guttate or plaque psoriasis, and 10 healthy controls. To avoid age-related bias, age matching was performed for each group. Circulating levels of interferon (IFN)-gamma, interleukin (IL)-1RA, IL-2, IL-12p40, IL-17A, IL-22, and IL-23 were measured with an enzyme-linked immunosorbent assay (ELISA). Psoriasis-affected tissue was obtained through biopsy sampling from the eight patients who exhibited the most typical morphology. Levels of IL-1RA, IL-12p40, IL-17, IL-22, and IL-23 in the psoriasis tissue samples were measured with western blot analysis. RESULTS: ELISAs of the serum samples showed higher levels of inflammatory cytokines such as IL-1RA, IL-2, IL-23, and IFN-gamma in patients with psoriasis than in healthy controls. However, the inflammatory cytokine levels did not differ significantly between guttate and plaque psoriasis patients. Western blot analysis of psoriatic tissue revealed higher protein levels of Th-1- and Th-17-related cytokines in patients than in healthy controls. The levels of IL-12p40 and IL-23 were unexpectedly higher in plaque tissue than in guttate tissue. CONCLUSION: The morphological phenotype of psoriasis does not appear to be determined by a specific activation of either the Th-1 or Th-17 pathway. Rather, the cytokine profile influences disease activity and is altered according to the status of the lesion (early or chronic).
Bias (Epidemiology) ; Biopsy ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interferons ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-12 Subunit p40 ; Interleukin-17 ; Interleukin-2 ; Interleukin-23 ; Interleukins ; Phenotype ; Population Characteristics ; Psoriasis*

OBJECTIVES: Respiratory epithelial cells are the first site of interaction of allergens with the immune system. The aim of this study was to examine the effect of epithelial cells, which were stimulated with house dust mite (HDM) extracts, on the immune response of peripheral blood mononuclear cells (PBMCs). METHODS: Primary nasal polyp epithelial cells were exposed to dermatophagoides pteronyssinus and dermatophagoides farina for 48 hr, and then the supernatant and cells were collected. After stimulation with HDM extract, the epithelial cells were co-cultured with PBMCs for 72 hr and then the supernatant was collected. We measured the interleukin (IL)-8 and granulocyte-macrophage colony stimulating factor to determine the activation of the epithelial cells. The tumor necrosis factor (TNF)-alpha, IL-5 and interferon-gamma were measured to evaluate the interaction between the epithelial cells and the PBMCs. The mRNA expression of intercellular adhesion molecule 1 (ICAM-1) was assessed using the anti-ICAM-1 antibody. RESULTS: The HDM extracts activated the nasal epithelial cells and enhanced the expression of ICAM-1 mRNA and cell membrane ICAM-1. When the activated epithelial cells were co-cultured with PBMCs, the PBMCs produced lager amounts of TNF-alpha and IL-5. However the cytokine production was not inhibited by pretreatment with ICAM-1 antibody. CONCLUSION: HDM allergens induce allergic inflammation by activating nasal epithelial cells, yet the interaction of the epitheila cells and the PBMCs may not be associated with an ICAM-1 medicated mechanism.
Allergens ; Cell Membrane ; Colony-Stimulating Factors ; Dermatophagoides pteronyssinus ; Dust ; Epithelial Cells ; Immune System ; Inflammation ; Intercellular Adhesion Molecule-1 ; Interferon-gamma ; Interleukin-5 ; Interleukins ; Nasal Polyps ; Pyroglyphidae ; RNA, Messenger ; Tumor Necrosis Factor-alpha

STUDY DESIGN: Prospective randomized clinical trial. OBJECTIVES: To determine the minimal effective pretreatment dosage of recombinant human erythropoietin for preoperative autologous donation in lumbar stenosis surgery. SUMMARY OF LITERATURE REVIEW: Preoperative autologous donation is one of the most widely used methods of autotransfusion. However securing predetermined amount may be difficult due to falling hematocrit with repeated donation especially in patients with low basal hematocrit. In this situation recombinant human erythropoietin(Epoetin alfa) may be used. MATERIALS AND METHODS: Forty five lumbar stenosis patients requiring posterior wide decompression and posterolateral fusion with instrumentation, who had basal hematocrit less than 40% were selected and alloted randomly into 3 groups. Group I(n=15) had pretreatment with Epoetin alfa 50 unit/kg. Group II(n=15) was pretreated with 25 unit/kg. Group III(n=15) had no pretreament. Patients were excluded from donation when their hematocrit values were less than 33%. RESULTS: The mean number of units collected per patient(mean+/-SD) was 3 for group I(P<0.05), 2.84 for group II and 2.67 for the control group. The red cell volumes in pretreated groups(347 ml, 325 ml) were greater than in group III(255 ml, P<0.05). The differences between hematocrits of the first and the third preoperative donations were significantly less in group I(1.50) and group II(1.51) than that of control group(3.73). Two patients in group II and 3 patients in group III required additional homologous transfusion postoperatively. And there were no significant differences in the pattern of postoperative changes of hemoglobin among the groups. There were no significant differences in amount of intraoperative saved blood, postoperative reinfused blood, and postoperative drainage. CONCLUSION: Fifty units/kg of Epoetin alfa seems to be more effective than twenty-five units/kg for preoperative autologous donation in patients requiring posterior wide decompression, posterolateral fusion with instrumentation.
Blood Transfusion, Autologous ; Cell Size ; Constriction, Pathologic* ; Decompression ; Drainage ; Erythropoietin* ; Hematocrit ; Humans* ; Prospective Studies ; Epoetin Alfa

PURPOSE: Compared with the practice of administrating subcutaneous erythropoietin injection two or three times a week in end-stage renal failure, a weekly administration reduces the frequency of injection and the workload in renal units. We investigated whether subcutaneous epoetin alfa administered weekly was as effective as the same weekly dosage given in two or three divided doses. METHODS: Eighty-three patients were randomized to treatment with subcutaneous epoetin alfa either once a week (n=44), or to their original dosage two or three times a week (control, n=39) for 12 weeks. If hemoglobin was out of range (9.0-12.0 g/dL), the dosage was changed. RESULTS: Mean hemoglobin levels at randomization and after 4, 8 and 12 weeks were 10.7, 11.1, 11.3 and 11.0 g/dL, respectively, in the once weekly group compared with 10.5, 11.3, 11.5 and 11.3 g/dL, respectively, in the control group. The mean weekly epoetin alfa dosage at randomization and after 4, 8 and 12 weeks were 142.8, 123.0, 116.7 and 112.3 IU/kg, respectively, in the once-a-week group compared with 128.4, 119.3, 103.5 and 101.2 IU/kg, respectively, in the control group. No statistically significant differences between the groups were apparent in changes in hemoglobin levels or epoetin alfa dosages at week 12. There was no significant difference between the groups in number of patients who maintained stable hemoglobin levels without epoetin alfa dose increases. CONCLUSION: This study demonstrates that a weekly subcutaneous administration of epoetin alfa is as effective and safe as injecting it two or three times a week administration in maintaining hemoglobin levels in stable hemodialysis patients.
Anemia ; Erythropoietin ; Humans ; Kidney Failure, Chronic ; Random Allocation ; Renal Dialysis ; Epoetin Alfa

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is an essential and well-established treatment for renal anemia. Rcently, clinicians have moved toward administration of high dose rHuEPO to reduce the inconvenience and time efficient.We aimed to determine whether high dose subcutaneous (SC) epoetin alfa is as efficient and safe as the usual dose for treating anemia in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Twenty-four patients on CAPD were randomly assigned to a high-usual dose group (n=12) and an usual-high dose group (n=12) with a variable interval for 48 weeks. Patients received 10 times treatments by scheduled visiting during Period I lasting 24 weeks and received 4 times treatments by scheduled visiting in Period II lasting 24 weeks by cross-over. The high dose was 10,000 IU and the usual dose was 4,000 IU epoetin alfa regimen. If hematocrit was out of the targeted range, 30~39%, the interval of epoetin alfa was changed within 50% of the previous interval. RESULTS: Fifteen patients, out of 24, completed the study (8 patients in the high-usual dose group; 7 patients in the usual-high dose group). Mean hemoglobin levels at randomization and after 12, 24, 36 and 48 weeks were 10.8+/-1.1, 11.5+/-0.9, 11.5+/-1.5, 11.4+/-1.5, 11.5+/-0.8 g/dL, respectively, in high-usual dose group compared with 11.2+/-0.8, 11.4+/-1.2, 11.2+/-0.9, 11.2+/-1.4, 11.4+/-0.9 g/dL, respectively, in usual-high dose group. The mean weekly epoetin alfa dosages at randomization and after 12, 24, 36 and 48 weeks were 83.6+/-38.1, 87.1+/-35.8, 89.4+/-34.2, 60.1+/-25.1, 62.8+/-30.7 IU/kg/week, respectively, in high-usual dose group compared with 69.8+/-31.6, 64.9+/-12.2, 69.9+/-46.1, 78.8+/-29.3, 75.9+/-16.4 IU/kg/week, respectively, in usual-high dose group. No statistically significant differences between the two groups were apparent for hemoglobin levels or mean weekly epoetin alfa dosages. Treatment interval at Period I and Period II were 13.3+/-5.3, 8.2+/-4.3 days in high-usual dose group compared with 7.0+/-2.5, 13.4+/-4.0 days in usual-high dose group with statistically significant differences. Treatment interval in high dose was about two times as longer as usual dose. Adverse events were generally mild and transient, and pain on injection site following subcutaneous administration was rarely reported. CONCLUSIONS: This study demonstrates that epoetin alfa 10,000 IU is as efficient and safe as 4,000 IU with a similar weekly dose in CAPD patients. Epoetin alfa 10,000 IU administration can reduce frequency of injections by about one half.
Anemia ; Cross-Over Studies* ; Erythropoietin ; Hematocrit ; Humans ; Peritoneal Dialysis, Continuous Ambulatory* ; Random Allocation ; Epoetin Alfa