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Elevated levels of arginine vasopressin (AVP) have been reported to be involved in the pathogenesis of heart failure (HF). Recent evidence has shown the role of copeptin, the C-terminal fragment of pro-AVP, as a biomarker in patients with HF. However, the relevant information is still limited. Therefore, we evaluated 39 Japanese patients admitted for HF between 2013 and 2015 (23 males and 16 females with an average age of 79.2 years). They were treated according to the Japanese acute HF guideline. Plasma copeptin levels were measured on admission and about 1 week later. The median plasma copeptin levels on admission were 0.5 (0.1-50.6) pmol/L, higher than the normal values (0.24 ± 0.06 pmol/L). Despite the similar clinical severity on admission, the patients showed great variability in plasma copeptin levels. They were divided into three groups (13 patients/group) according to plasma copeptin levels on admission: highest (> 30.8 pmol/L), midrange, and lowest (< 0.2 pmol/L) groups. Initial treatment improved HF symptoms in 37 of 39 patients, with the two unresponsive patients in the lowest group. Notably, plasma copeptin responses to initial treatment were different, depending on admission copeptin levels. The initial treatment significantly decreased copeptin levels in the highest group, but increased copeptin levels in the lowest group. By contrast, patients in the midrange group showed no significant changes. Thus, the treatment appears to restore the plasma copeptin levels. In conclusion, HF is a complex syndrome with the differential integration of stimulatory and inhibitory inputs to the AVP/copeptin secretory system.

Thymosin β4 (Tβ4) is a major intracellular G-actin-sequestering peptide. There is increasing evidence to support important extracellular functions of Tβ4 related to angiogenesis, wound healing and cardiovascular regeneration. We investigated the expression of 'Tβ4' and 'thymosin β10', a closely related peptide, during skeletal muscle regeneration in mice and chemotactic responses of myoblasts to these peptides. The mRNA levels of 'Tβ4' and 'thymosin β10' were up-regulated in the early stage of regenerating muscle fibres and inflammatory haematopoietic cells in the injured skeletal muscles of mice. We found that both Tβ4 and its sulphoxized form significantly accelerated wound closure and increased the chemotaxis of C2C12 myoblastic cells. Furthermore, we showed that primary myoblasts and myocytes derived from muscle satellite cells of adult mice were chemoattracted to sulphoxized form of Tβ4. These data indicate that muscle injury enhances the local production of Tβ4, thereby promoting the migration of myoblasts to facilitate skeletal muscle regeneration.

Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers.A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted.This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011.The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease.The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

The effects of sevoflurane on proinflammatory cytokines related to ischemic-reperfusion injury are not clear. The hypothesis was tested that sevoflurane decreases myocardial ischemic-reperfusion injury by suppressing proinflammatory cytokines.Prospective, randomized study.A medical university heart center.Twenty-three patients undergoing coronary artery bypass surgery allocated randomly into 2 groups.Anesthesia for 23 patients undergoing coronary artery bypass surgery was maintained using either fentanyl (30 microg/kg) with propofol (2-8 mg/kg/h) in the control group (n = 10) or fentanyl (30 microg/kg) with 0.5% to 1.0% sevoflurane in the sevoflurane group (n = 13).Interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) were measured by enzyme-linked immunosorbent assay. Troponin-T and creatine kinase-MB isoenzyme (CK-MB) were measured by enzyme immunoassay and ultraviolet absorption spectrophotometry, respectively. Serum IL-6 and IL-8 concentrations in both groups increased significantly over baseline from 60 minutes after declamping the aorta (p0.001). The increases were greater in the control group than in the sevoflurane group (p0.05). Serum IL-10 and IL-1ra concentrations in both groups increased significantly over baseline from 60 minutes after declamping the aorta (p0.001). There were no differences between the two groups. Serum troponin-T and CK-MB concentrations increased significantly in both groups from 60 minutes after declamping the aorta (p0.001); the increases were greater in the control group (p0.05).Sevoflurane suppressed the production of IL-6 and IL-8, but not IL-10 and IL-1ra. Changes in the balance between pro- and anti-inflammatory cytokines may be one of the most important mechanisms of myocardial protection caused by sevoflurane.

Nicorandil (NCR), a KATP channel opener, has been reported to preserve microvascular integrity in patients with reperfused myocardial infarction. We tested the hypothesis that NCR suppresses myocardial ischemia and reperfusion injury via the attenuation of cytokine production. Forty patients who underwent coronary artery bypass graft surgery were studied. The patients were randomly divided into two groups, i.e., the patients with NCR (4-6 mg/h; N group, n = 20) or without NCR (C group, n = 20). Cardiac surgery was performed under anesthesia using fentanyl and propofol. Blood were sampled at the time of induction of anesthesia, pre-cardiopulmonary bypass, 60 min after aortic occlusion, and 60, 120, and 180 min after declamping the aorta. The activation of NF-kappaB, expression of adhesion molecules, and cytokine production were evaluated in blood samples from the control volunteers by flow cytometric analysis with or without lipopolysaccharide (LPS) stimulation in vitro. Serum IL-6 and IL-8 levels in both groups increased 60 min after declamping the aorta compared with the preoperative value (P < 0.001); the increases of these parameters in N group were lower than those in C group (P < 0.05). Serum creatine kinase with muscle and brain subunits and troponin-T levels increased 60 min after declamping the aorta in two groups (P < 0,001), but the increases of both parameters in N group were lower than those in C group (P < 0.05). NF-kappaB activation, CD11b/CD18 expression, and the production of TNF-alpha, IL-8, and IL-6 in monocytes and granulocytes were inhibited by NCR in vitro. NCR suppressed the increase of inflammatory cytokines such as IL-6 and IL-8 levels, and reduced myocardial reperfusion injury. The inhibition on NF-kappaB activation, adhesion molecule expression, and cytokine production may be one of the important mechanisms of myocardial protection of NCR.

In the dystrophin-mutant mdx mouse, an animal model for Duchenne muscular dystrophy (DMD), damaged skeletal muscles are efficiently regenerated and thus the animals thrive. The phenotypic differences between DMD patients and the mdx mice suggest the existence of factors that modulate the muscle wasting in the mdx mice. To identify these factors, we searched for mRNAs affected by the mdx mutation by using cDNA microarrays with newly established skeletal muscle cell lines from mdx and normal mice. We found that in the mdx muscle cell line, 12 genes, including L-arginine:glycine amidinotransferase and thymosin beta4, are up-regulated, whereas 7 genes, including selenoprotein P and a novel regeneration-associated muscle protease (RAMP), are down-regulated. Northern blot analysis and in situ hybridization revealed that RAMP mRNA is predominantly expressed in normal skeletal muscle and brain, and its production is enhanced in the regenerating area of injured skeletal muscle in mice. RAMP expression was much lower in individual muscle cell lines derived from biopsies of six DMD patients compared to a normal muscle cell line. These results suggest that RAMP may play a role in the regeneration of skeletal muscle and that its down-regulation could be involved in the progression of DMD in humans.

Complementary DNAs coding for two subunits of hamster interleukin-12 (IL-12), p35 and p40, were cloned from a hamster dendritic cell (DC) cDNA library. The cloning demonstrated that hamster IL-12 consisted of a p35 subunit with 216 amino acid (aa) residues and a p40 subunit with 327 aa. Structural comparison of hamster p35 and p40 at the protein level showed the highest homologies with each counterpart of sigmodon (hispid cotton rat). The gene expressions of hamster IL-12 p35 and p40 in bone marrow (BM) cells cultured in the presence of mouse granulocyte macrophage-colony-stimulating factor (mGM-CSF) and IL-4 were up-regulated during culture. Immunoblot analysis of 293 cells transfected with hamster p35 and p40 expression vectors suggested the presence of a covalently linked p35/p40 heterodimer. Furthermore, supernatant from the 293 cells transfected with both expression vectors induced the up-regulation of interferon-gamma (IFN-gamma) mRNA in hamster splenocytes, indicating that the p35/p40 heterodimer IL-12 protein present in the supernatant was functional. These results suggest that the vectors containing hamster IL-12 cDNA might be suitable tools for developing an immunotherapeutic approach against experimental cancer in a hamster model.

Because the prognosis of patients with pancreatic cancer is very poor, development of a novel approach for treatment of this disease is vital. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy against established syngeneic hamster pancreatic cancer named HPD1NR. Hamster enriched DCs were prepared from bone marrow (BM) by a culture for 7 days in the presence of mouse GM-CSF and mouse IL-4, and characterized by the expression of specific DC markers (DEC205, DC-SIGN) mRNA using in situ hybridization (ISH). DCs pulsed with tumor lysate and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) or DCs alone were injected s.c. weekly into HPD1NR-bearing hamsters three times. Tumor growth was significantly inhibited by 82% in hamsters treated with tumor lysate and DOTAP-pulsed DCs when compared with the PBS vehicle-treated group. These findings suggest that DC-based immunotherapy may be a useful approach for the treatment of pancreatic cancers.

Background The beneficial effect of inhaled nitric oxide (NO) on pulmonary hypertension is well known. However, the indications for NO inhalation therapy for pulmonary hypertension associated with congenital heart lesions are still unclear. The aim of the current study was to seek a measure that would predict the effectiveness of inhaled NO in infants undergoing cardiac surgery. Methods Forty-six infants with pulmonary hypertension were studied. Pulmonary vascular resistance (PVR) measured at the time of cardiac catheterization was used as an indicator and compared with pulmonary arterial pressure/systemic blood pressure ratio (Pp/Ps) at the time of weaning from cardiopulmonary bypass. The effect of 40 ppm of inhaled NO for 15 min was evaluated in patients whose Pp exceeded systemic values. Results Preoperative PVR correlated positively with Pp/Ps at the time of weaning from cardiopulmonary bypass (r2 = 0.86; P < 0.05; n = 46). A Pp/Ps greater than or equal to 1 was not observed in any cases in which the preoperative PVR values were less than 7 Wood units m2; Pp/Ps ratio greater than or equal to 1 occurred in four patients. Each of these had PVR values greater than 7 Wood units m2. Three of these patients who had PVR values in the 7-12 Wood units m2 range were responsive to inhaled NO. The fourth patient, whose PVR value was greater than 15 Wood units m2, was unresponsive. Lung biopsy specimens were obtained in two patients whose preoperative PVR values were greater than 10 Wood units m2. Conclusion Preoperative PVR correlates reasonably well with postbypass Pp/Ps.

Objective Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. Design A nationwide retrospective study. Setting 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. Participants This study included patients ≥18 years diagnosed with ‘classical fever of unknown origin’ (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. Results A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19–94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. Conclusions With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

Menin is a protein product of a tumor supressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome. We isolated rat menin cDNA clones from a fetal rat brain cDNA library. We also determined the nucleotide sequence of the protein coding region of mouse menin cDNA, which was partly registered in the expressed sequence tag (EST) database. Deduced amino acid sequences of rat and mouse menin are highly homologous to human menin. All of the previously reported disease-associated missense mutations and single amino acid deletions were observed at the residues that are conserved among these three species. Rat MEN1 transcripts were detected not only in the endocrine tissues but also in the tissues of the nervous, digestive, reproductive and immune systems. The MEN1 transcripts were abundantly expressed in the developing rat brain on day 14–18 of gestation. Immunoblotting and immunocytochemical analysis of the COS-7 cells transfected with a rat menin-expression vector revealed that the translated product has a molecular mass of approximately 70 kDa, and is localized mainly in the nucleus. These findings are consistent with those reported on human menin.

In the dystrophin-deficient mdx mice, an animal model of Duchenne muscular dystrophy (DMD), damaged skeletal muscles are efficiently regenerated and thus the animals thrive. The phenotypic differences between DMD patients and mdx mice suggest the existence of factors that modulate the muscle wasting in the mdx mice. To identify these factors, we searched for mRNAs affected by the mdx mutation using cDNA microarrays with newly established skeletal muscle cell lines derived from mdx and normal mice. We found that genes encoding thymosin beta4, frizzled related protein 2 (FRP2), and regeneration-associated muscle protease (RAMP) are up-regulated in skeletal muscle of mdx mice. Thymosin beta4 was induced in both regenerating muscle fibers and inflammatory cells after muscle injury. It stimulated migration and chemotaxis of myoblasts. FRP2 was dramatically induced upon muscle injury. RNA interference-mediated knockdown of FRP2 mRNA in myoblasts resulted in a massive cell death. Thus FRP2 may enhance the survival rate of myoblasts in the regenerative regions. RAMP mRNA was specifically induced in the regenerating areas of injured skeletal muscle. Expression of RAMP and FRP2 was much lower in individual muscle cell lines derived from biopsy specimens from several DMD patients compared to in a normal muscle cell line. Above results suggest that thymosin beta4, FRP2, and RAMP may play roles in the regeneration of skeletal muscle and that down-regulation of these molecules could be involved in the progression of DMD in humans.

Many human leukocyte antigen (HLA)-class I (mainly A*0201)-restricted peptide-specific cytotoxic T cells (CTLs) have been derived from peripheral blood lymphocytes (PBLs) of melanoma patients. However, few studies regarding HLA-A*2402-restricted melanoma-associated peptides have been performed, because HLA-A24 is not a common allele in Caucasians. In this study, we investigated the specific CTL-inducing activity of 5 HLA-A*2402-restricted peptides derived from gp100, tyrosinase, MAGE1, MAGE2 and MAGE3. A CTL induction culture was performed using PBLs and cultured dendritic cell (DC) pulsed with HLA-A*2402-restricted melanoma peptide cocktail. The CTLs derived from volunteers killed the A24 peptide-pulsed TISI cells and even HLA-A*2402-positive melanoma cells, but not HLA-A*0201-positive cells. IFN-gamma levels produced by the melanoma patients' CTLs were obviously low in each peptide group compared with those produced by the volunteers' CTLs, which indicated the presence of immunosuppressive factors in metastatic melanoma. These results suggested that polyvalent immunotherapy using multiple epitopes from melanoma antigens might be a better way of improving the efficacy of treatment.

DEC-205, a putative antigen uptake receptor, belongs to a family of transmembrane C-type lectins. This molecule is known to be one of the most authentic markers for the lineage of dendritic cells. In the present study, we determined the primary structure, tissue distribution and cellular localization of hamster DEC-205. The multi-domain structure of mouse and human DEC-205 was completely conserved in hamster with the overall identity of approximately 80%. DEC-205 transcripts were detected in the thymus and bone marrow cells cultured in the presence of mouse granulocyte macrophage colony-stimulating factor and interleukin-4 in which the DEC-205 expression was up-regulated in the course of cultures. Hamster DEC-205 was mainly detected on cell membrane and shown to mediate the uptake of flourescein isothiocyanate-conjugated ovalbumin. DEC-205 is a highly conserved molecule across the species suggesting its fundamental role in the immune system.

We selected three human cancer cell lines [human melanoma (SEKI), human melanoma (G361), and human neuroepithelioma (NAGAI)] that have an ability to develop cancer cachexia syndrome with and without accompanying anorexia and examined the hypothalamic levels of mRNAs for neuropeptide Y (NPY), melanin-concentrating hormone, and orexin. The body weight of sham-operated mice continued to increase, while mice of all tumor-bearing groups lost weight. Competitive reverse transcription-polymerase chain reaction analysis showed that, regardless of feeding status, NPY mRNA levels were elevated in all tumor-bearing mice compared with sham-operated mice, although to a lesser degree than weight-matched pair-weight mice. Melanin-concentrating hormone and orexin mRNA in the hypothalamus followed the same pattern as NPY, although most of the differences did not reach statistical significance. These results support the notion that the response of NPY mRNA to a negative energy balance is less sensitive in these rodent models of cancer cachexia.

MUCI protein is widely expressed on various human cancer cells and has a specific highly glycosylated core structure with multiple tandem repeats, which may include an immunogenic peptide sequence. The potency of MUC1 protein to induce human histocompatibility leukocyte antigen-class I-restricted cytotoxic T-lymphocyte (CTL) induction remains to be fully clarified in human beings. In the current study, we made MUCI-expressing human dendritic cells (DCs) using recombinant adenovirus vector. Adenovirus vector plasmid containing human MUCI cDNA, pAdHM4-MUC1 was constructed using in vitro ligation with a shuttle vector, pHMCMV5. Adenovirus vector expressing MUCI was generated by the transfection of PacI-digested recombinant vector plasmid into 293 cells. Human blood DCs were obtained from 7-day culture of monocytes with recombinant human (rh) granulocyte-macrophage (GM) colony-stimulating factor (CSF) and (rh)interleukin (IL)-4. Then, I x 10 6 DCs were incubated with viral supernatant at a multiplicity of infection of 200 for 24 h in the presence of rhGM-CSF and rhlL-4. Flow cytometric analysis showed that 30% to 40% of the transduced DCs expressed MUCI protein; by contrast, nontransduced or transduced DCs with mock virus expressed only small amounts of MUC1 protein. Adenovirus-mediated MUCI gene transduction into DCs had no significant effect on DC surface marker expressions or functions such as mixed leukocyte reaction. Furthermore, MUCI-specific CD8 + CTLs could be induced from healthy donor blood lymphocytes using MUCI-expressing DCs as stimulators. These results suggested that MUCI gene-transduced DCs are a functional and potent tool for triggering a CTL response against MUC1 + cancer cells.

Menin is a protein product of a tumor supressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome. We determined the nucleotide sequence of the Drosophila menin cDNA using RT-PCR and RACE, and confirmed it by direct sequencing of genomic DNA. Gene expression of Drosophila menin was detected by Northern blot analysis in adult and embryo as two types of transcripts, one identical in size to the cDNA, and the other larger but detected only in embryo. The Drosophila menin gene was composed of five exons in which the protein was encoded in exon 2 through 5, and spanned approximately 6.3 kb. The deduced amino acid (AA) sequence of Drosophila menin consisted of 751 AAs with a calculated molecular mass of 81.7 kDa, and showed 44–47% identity to human, rat, mouse and zebrafish menin over the entire length. Among the AA residue substitutions that have been reported as disease-associated missense mutations and single AA deletions, 53 out of 71 were completely conserved in Drosophila. The presence of menin ortholog in insect indicates that menin is an evolutionally conserved protein with a fundamental role in biological processes.

To determine the influence of prostaglandin E1 (PGE1) on the cytokine balance and myocardial protection during cardiac surgery.Prospective, randomized, nonblinded study.University hospital.A total of 19 patients on cardiopulmonary bypass undergoing cardiac surgery.According to randomized sequence, the patients received PGE1 (0.02 approximately 0.05 microg x kg(-1) x min(-1)) from the beginning of surgery to the end of study (PGE1 group, n = 11) or nothing (control group, n = 8).Interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor I (sTNF RI), and soluble tumor necrosis factor receptor II (sTNF RII) were measured by enzyme-linked immunosorbent assays. Troponin-T and isoenzyme of creatine kinase with muscle and brain subunits (CK-MB) were measured by enzyme immunoassay and ultraviolet absorption spectrophotometry method, respectively. Serum IL-6 and IL-8 concentrations in both groups increased significantly from 60 mins after declamping the aorta compared with preoperative value (p.001), However, the increases were greater in the control group than in the PGE1 group (p.01). Serum IL-10, IL-1ra, sTNF RI, and sTNF RII concentrations increased significantly from 60 mins after declamping the aorta compared with preoperative values in two groups (p.001, respectively). There were no differences between the two groups. Serum troponin T and CK-MB concentrations increased significantly in the two groups from 60 mins after declamping the aorta (p.001), but these increases were greater in the control group than in the PGE1 group (p.01). IL-6 and IL-8 levels correlated with CK-MB concentration (r2 = 0.49, r2 = 0.36; p.001 respectively).PGE1 suppressed the production of IL-6 and IL-8 but not IL-10, IL-1ra, sTNF RI, or sTNF RII. The change in the balance between pro-and anti-inflammatory cytokines may be one of the most important cytoprotective mechanisms of PGE1.

OBJECTIVE To determine the influence of methylprednisolone on the cytokine balance during cardiac surgery. DESIGN Prospective, randomized, nonblinded study. SETTING University hospital. PATIENTS Twenty-one patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. INTERVENTIONS According to a randomized sequence, the patients either received methylprednisolone (30 mg/kg) [corrected] before cardiopulmonary bypass and before declamping of the aorta (MPS group, n = 11) or received nothing (control group, n = 10). MEASUREMENTS AND MAIN RESULTS Serum proinflammatory cytokines (interleukin [IL]-8, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra) were measured by enzyme-linked immunosorbent assays. Serum IL-6 and IL-8 concentrations in the control group (15.2 +/- 4.1 and 14.1 +/- 1.9 pg/mL, preoperatively) increased to 242 +/- 70.1 and 97.3 +/- 18.3 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). The increases were greater than those from 2.5 +/- 0.6 and 2.5 +/- 0.5 pg/mL to 109.5 +/- 29.0 and 33 +/- 4.1 pg/mL in the MPS group for IL-6 and IL-8, respectively. Serum IL-10 concentrations increased significantly 60 mins after declamping of the aorta compared with its preoperative value in the two groups (the control group, from 1.0 +/- 0 to 537.9 +/- 61.7 pg/mL; the MPS group, from 0.3 +/- 0.2 to 654.9 +/- 24 pg/mL [p < .01, p < .01, respectively]). No difference was found between the two groups. Similarly, serum IL-1ra concentrations in the two groups increased the preoperative value in the control group from 304 +/- 120 to 44,374 +/- 14,631 pg/mL and in the MPS group from 616.5 +/- 109.6 to 35,598 +/- 9,074 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). There was no difference between the two groups. CONCLUSIONS Methylprednisolone reduces the production of IL-6 and IL-8 but not that of IL-10 and IL-1ra. These results suggest that one of the mechanisms of the cytoprotective effect of methylprednisolone may be to make changes in the proinflammatory and anti-inflammatory cytokine balance.