Does prefrontal cortex transcranial direct current stimulation influence the oxygen uptake at rest and post-exercise?

The study evaluated the effect of transcranial direct current stimulation (tDCS) applied over prefrontal cortex on the oxygen uptake (V˙ O2) at rest and during post-exercise recovery. The V˙ O2 was assessed in eleven healthy subjects before, during tDCS (sham or anodal tDCS, 2 mA, 20 min), and 30-min following isocaloric aerobic exercise (~200 kcal). During tDCS, no changes were observed on V˙ O2 compared to baseline (P=0.95) and sham condition (P=0.85). The association between isocaloric exercise and anodal tDCS increased the V˙ O2 throughout 30-min recovery compared to sham condition (P<0.001). Therefore, the energy expenditure within the excess post-exercise oxygen consumption (EPOC) period, after anodal tDCS was approximately 19% higher compared to the sham condition (P<0.05). In conclusion, anodal tDCS applied on the prefrontal cortex combined with submaximal aerobic exercise increased the EPOC, enhancing the V˙ O2 and energy expenditure at least for 30-min of recovery.

Synergism of BSF-2/interleukin 6 and interleukin 3 on development of multipotential hemopoietic progenitors in serum-free culture.

We investigated the effects of B cell stimulatory factor 2/interleukin 6 (BSF-2/IL-6) on the development of murine hemopoietic progenitors using serum-containing culture and serum-free culture. In serum-containing culture, BSF-2 mainly supported multipotential blast cell colonies from spleen cells of normal and 5-fluorouracil (5-FU)-treated mice. In serum-free culture, no colony growth was seen in the presence of BSF-2. Addition of BSF-2 to the serum-free culture containing IL-3 resulted in a significant increase in the number of colonies formed from multipotential progenitors in spleen cells and bone marrow cells of 5-FU-treated mice, whereas no effects were seen on the number of single or oligolineage colonies formed by the spleen cells of normal mice. These results suggested that BSF-2 and IL-3 act synergistically on the multipotential progenitors but not on the maturer progenitors. When BSF-2 was added to a culture containing low concentrations of IL-3 (1 U/ml, 4 U/ml), which had little effect on colony formation, the number of total colonies formed by the spleen cells and bone marrow cells of 5-FU-treated mice increased significantly. The combination of BSF-2 and 40 U/ml of IL-3 resulted in a significant enlargement of GMM colonies. Thus, BSF-2 appears to enhance the sensitivity of multipotential hemopoietic progenitors to IL-3.

The relationship between rating of perceived exertion and muscle activity during exhaustive constant-load cycling.

The aims of this study were to verify the relationship between rating of perceived exertion (RPE) and electromyography (EMG) increases during exhaustive constant-load cycling bouts and, to compare and to correlate the power outputs corresponding to perceived exertion threshold (PET) and neuromuscular fatigue threshold (NFT). 11 men completed 3-4 different exhaustive constant-load cycling bouts on a cycle ergometer, being RPE and EMG measured throughout the bouts. The linear regression of the RPEslope and EMGslope against the power output identified the PET and NFT intensity, respectively. There was a significant relationship between RPEslope and EMGslope (R(2)=0.69; P<0.01). However, the linearity of RPEslope (R(2)=0.93±0.07) was significantly higher (P<0.001) than EMGslope (R(2)=0.63±0.25). In addition, the RPEslope and EMGslope were related to time to exhaustion (r=-0.59 and r=-0.60; P<0.001). There was no significant difference (P=0.42) between PET (201.5±27.9W) and NFT (210.3±22.6W) and they were significantly correlated (r=0.78; P=0.005). Therefore, the RPE and EMG increases during exhaustive constant-load cycling bouts are related and, PET and NFT intensities are similar and closely associated.

Comparison of electromyography fatigue threshold in lower limb muscles in trained cyclists and untrained non-cyclists.

The purpose of this study was to identify and compare the Electromyographic Fatigue Threshold (EMG(FT)) determined in the Vastus Lateralis (VL), Rectus Femoris (RF), Biceps Femoris (BF), Semitendinosus (ST) and Tibialis Anterior (TA) during stationary cycling in trained cyclists and non-cyclists. Using a cycle ergometer, 13 cyclists (28.4 +/- 6.9 years; 70.3 +/- 13 kg; 176.1 +/- 8.5 cm) and 11 non-cyclists (25.8 +/- 4 years; 73 +/- 9.1 kg; 175 +/- 6.4 cm), performed a maximum incremental test (ITmax) (90 rpm) to determine the (EMG(FT)). Maximal power output (W(PEAK)) reached by cyclists was higher than for non-cyclists (372.6 W and 248.9 W respectively) (P < 0.01). For the five muscles analyzed in cyclists, EMG(FT) occurred at 85.7% of cases in the VL, 92.9% in RE 78.6% in BE 78.6% in ST and 50% in TA, while in the non-cyclists group, this occurrence was 100% to muscle VL, 100% to RF, 92.6% to BF, 78.6% to ST, and 78.6% to TA. Analyzing the percentage corresponding to the power at EMG(FT) in relation to W(PEAK) reached, no differences between groups were observed for RF, BF and ST, however VL and TA, as well as the mean from all muscles were lower for cyclists than non-cyclists (P < 0.05). The present results showed that EMG(FT) is more easily identified in RF and VL muscles for both groups, and it may be an interesting method to evaluate the adaptive responses from aerobic and anaerobic metabolisms during cycling training programs.

The efficiency of pedaling and the muscular recruitment are improved with increase of the cadence in cyclists and non-cyclists.

The objective of this study was to compare the efficiency of pedaling (EP) and the electromyographic activity (EMG) between cyclists and non-cyclists during cycling in different cadences. Using a cyclosimulator, 12 cyclists (26.5 +/- 4.5 years; 68.2 +/- 10.5 kg; 175.6 +/- 8.2 cm) and 9 non-cyclists (25.1 +/- 4.3 years; 72.6 +/- 9.8 kg; 174.6 +/- 6.2 cm), performed a maximum incremental test (ITmax), and subsequently, two constant load tests (Tconst) in different cadences (60 and 90 rpm) at the intensity of the electromyographic fatigue threshold (EMGth) determined in ITmax. Before the Tconst, the subjects performed a maximum isometric voluntary contraction (MIVC) for the normalization of the EMG data of Tconst. During Tconst, the EMG of the studied muscles was recorded, as well as the EP Although there was a trend of higher values in all occasions for the cyclists, there were no statistical differences in EP and the EMG when compared in a same cadence between groups. However, when the EMG is compared in different cadences in the same group, there was a significant increase (p < 0.05) in the muscles that work during the recovery phase with the increase in cadence, in both groups, being more evident in the cyclists. In conclusion, the hypothesis that cyclists had better technique than non-cyclists was not confirmed statistically. However, it was found that the increase in cadence improves the EP and the recruitment in both groups.

Impact of an ultrasound-guided radiofrequency ablation training program on the outcomes in patients with hepatocellular carcinoma.

PURPOSE: The aim of this study was to retrospectively evaluate the impact of a training program on the safety and efficacy of percutaneous ultrasound-guided radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 227 patients with 296 HCC nodules who underwent percutaneous RFA with or without transcatheter arterial chemoembolization at our institution were included. There were 163 men and 64 women with a mean age of 74.2±8.3 (SD) years (range: 41-89 years). Percutaneous ultrasound-guided RFA was performed by three trainees (205 HCC nodules in 157 patients) or a mentor (91 HCC nodules in 70 patients) after preprocedural preparation including planning ultrasonography. We compared background-related, tumor-related, and treatment-related factors, and local recurrence and complication rates between the trainee group and the mentor group. Similarly, we compared these variables among the years 2015, 2016, and 2017 for trainee group. RESULTS: The proportion of easy-to-treat tumors in the trainee group (109/205; 53.2%) was greater than that in the mentor group (33/91; 36.3%) (P=0.020). No significant differences were observed in procedure difficulty among the years 2015, 2016, and 2017 for trainee group (easy-to-treat HCC nodules: 25/47; 53.2% vs. 39/79; 49.4% vs. 45/79; 57.0%. P=0.775). The local recurrence rate in the trainee group was 8.8% (18/205 HCC nodules) which was equivalent to 7.7% in the mentor group (7/91 HCC nodules). No significant differences were observed in local recurrence rate (8.8% vs. 7.7%, respectively; P=0.621) and major complication rate (1.3% vs. 1.4%, respectively; P=0.999) between the trainee group and the mentor group. No significant differences were observed in local recurrence rates ([5/47; 10.6%] vs. [11/79; 13.9%] vs. [2/79; 2.5%]) (P=0.109) and major complication rates ([1/36; 2.8%] vs. [1/62; 1.6%] vs. [0/59; 0%]) (P=0.701) between the years 2015, 2016, and 2017 for trainee group. CONCLUSION: A well supervised training program that includes planning ultrasonography fosters the efficacy and treatment quality of RFA for HCC.

Behavior of emg activation of rectus femoris, vastus lateralis and vastus medialis muscles during maximum contraction before and after a series of repeated efforts.

The proposal of this study was to analyze the behavior of electromyographic activity of the Rectus Femoris, Vastus Lateralis and Vastus Medialis muscles during Maximum Isometric Voluntary Contraction (MIVC) performed before (MIVC-1) and after (MIVC-2) the series of repeated effort (four series of 12 repetitions) of the movement of extending the knee performed on an extending table with 80% of maximum load (1RM) during 15 seconds each MIVC. The participants were 10 soccer players (average age of 17.7 +/- 0.67, average corporal mass of 67.07 +/- 6.06 kg and average height of 174.6 +/- 4.98 cm). Surface electrodes (disposable) were used. The frequency established was 1024 Hz (Low/High pass at 600/10 Hz). The statistical treatment employed analysis of variance (ANOVA) for repeated measurements followed by the HSD post hoc test of Tukey. The level of significance adopted for all analyses was p < 0.05. For the Rectus Femoris muscle the value expressed in RMS referring to MIVC-1 was 346.97 +/- 63.93 and MIVC-2 was 287.58 +/- 61.03 (p = 0.06) corresponding to 82.88% of MIVC-1. Regarding the Vastus Lateralis muscle the value in MIVC-1 was 385.50 +/- 120.23 and in MIVC-2 it was 316.87 +/- 67.85 (p = 0.04) corresponding to 82.19% of MIVC-1. For the Vastus Medialis muscle MIVC-1 value was 430.88 +/- 84.23 and MIVC-2 was 396.32 +/- 70.40 (p = 0.03) corresponding to 91.97% of MIVC-1. Results demonstrated that the muscles presented action potencies during the actions performed, being greater in MIVC-1. The Rectus Femoris muscle presented electromyographic signals of lesser amplitude than the Vastus Lateralis and Vastus Medialis muscles. The Vastus Medialis muscle presented a greater percentage value between MIVC-1 and MIVC-2. The Rectus Femoris muscle was the first to present signs of fatigue.

Interleukin 6 perfusion stimulates reconstitution of the immune and hematopoietic systems after 5-fluorouracil treatment.

Effects of interleukin 6 (IL-6) on the functional capacity of the immune and hematopoietic systems in 5-fluorouracil (5-FU)-treated mice were determined. IL-6 (5 x 10(4) units/mouse/day) was administered s.c. for 7 days by implantation of an osmotic pump, since it was demonstrated that a much higher increase in the primary response to sheep RBC was observed by administration of slowly released rather than daily s.c. injection of IL-6. IL-6 perfusion significantly augmented anti-sheep RBC antibody responses depressed by 5-FU (150 mg/kg) treatment. IL-6 also was shown to stimulate hematological recovery in mice treated with 5-FU. Namely, IL-6 perfusion accelerated the recovery of the number of hematopoietic stem cells, granulocyte-macrophage progenitors, and mature neutrophils in the spleen, although IL-6 did not stimulate the recovery of the neutrophil count in blood. Recovery of the platelet count in blood was stimulated by IL-6. Furthermore, it was found that the endogenous IL-6 level in serum increased after 5-FU treatment, which suggests that IL-6 may play some role in the recovery of the immune and hematopoietic systems. Finally, we examined the effect of IL-6 on the survival of mice treated with a higher dosage of 5-FU (300 mg/kg). IL-6 perfusion produced a distinct increase in survival rate at Day 30 (74% versus 28%). It is of note that the number of bacteria (identified as Escherichia coli) cultured from the spleen and the liver decreased in IL-6-perfused mice. This IL-6-induced effect was accompanied by enhancement of an oxidative burst response. Moreover, the anti-E. coli antibody titer in serum was higher in IL-6-perfused mice than in control mice. These results suggest the possible use of IL-6 for stimulating the reconstitution of the immune and hematopoietic systems after chemotherapy treatment.

Synergistic regulatory effects of interleukin 6 and interleukin 1 on the growth and differentiation of human and mouse myeloid leukemic cell lines.

We analyzed the effect of recombinant human interleukin 6 (IL-6), in combination with human recombinant interleukin 1 alpha (IL-1 alpha), on the growth and differentiation of several human and mouse myeloid leukemic cell lines, specifically U937, HL-60, M1, and its subclone M1-3b-N, into macrophage-like cells. IL-6 and IL-1 inhibited the growth of U937, M1, and M1-3b-N in a dose-dependent manner. Treatment of these cells with both IL-6 and IL-1 resulted in either an additive or a synergistic growth inhibition. IL-6 alone induced moderate differentiation of U937 and M1-3b-N, but the combination of IL-6 and IL-1 synergistically augmented this differentiation. In M1, only the combination of IL-1 and IL-6 resulted in differentiation. These two cytokines, whether alone or in combination, did not influence the growth and differentiation of HL-60. Therefore IL-6 in conjunction with IL-1 can induce differentiation in several human and mouse myeloid leukemic cell lines, although this effect varies with cell type. IL-6 did not stimulate the expression of IL-1 mRNA or IL-1 activity in U937 cells. IL-1 also failed to stimulate IL-6 production. Furthermore, the differentiation of U937 cells induced by IL-6 was not neutralized by antibody against either IL-1 alpha or IL-1 beta. The minimal differentiative effect of IL-1 was not affected by anti-IL-6 antibody. Therefore IL-6 and IL-1 appear to provide distinct signals for differentiation.

Effect of interleukin 6 (IL-6) on the differentiation and proliferation of murine and human hemopoietic progenitors.

We examined the effect of human recombinant (r) interleukin 6 (IL-6) on the differentiation of murine and human hemopoietic progenitors. Human IL-6 supported colony formation by murine bone marrow cells. These colonies consisted of neutrophils and macrophages. Recombinant IL-6 was able to support multilineage colony formation by spleen cells from 5-fluorouracil (5-FU)-treated mice. These colonies consisted of greater than 1 x 10(4) cells. Differential counts revealed large colonies exhibiting different combinations of cell lineages: neutrophils, macrophages, eosinophils, mast cells, and megakaryocytes. However, when blast cell colonies supported by interleukin 3 were replated into secondary dishes containing IL-6, they could differentiate into only neutrophils and macrophages. Single cells transferred from blast cell colonies formed only neutrophil/macrophage colonies. These results indicate that IL-6 had a direct effect on the growth and development of murine granulocyte-macrophage progenitors at a late stage and a significant effect on multipotential hemopoietic precursors that might be indirect through other cells. By contrast, human rIL-6 did not support colony formation by human bone marrow mononuclear cells. IL-6 may not show an independent activity for human hemopoiesis of myeloid lineage. However, the synergistic activity of IL-6 remains to be clarified.

A novel aspect of the maturational step of megakaryocytes in thrombopoiesis: bundle formation of microtubules in megakaryocytes.

We demonstrated bundle formation of microtubules both in the cytoplasmic processes and in the cytoplasm near the nucleus of cultured megakaryocytes by means of electron and immunofluorescent microscopy. To determine whether this bundle formation was related to megakaryocyte maturation, we studied the effects of recombinant human interleukin-6 (rhIL-6) in vitro and in vivo on this event. About 75% of the megakaryocytes in the bone marrow had no fibrous microtubule structures in the cytoplasm (type I), and about 25% had bundles of microtubules (type II). The formation of these bundles was promoted by rhIL-6 both in vitro and in vivo. Considerably more megakaryocytes cultured with recombinant murine (rm) IL-3 and rhIL-6 became type II than those cultured with rmIL-3 alone. Megakaryocytes from mice given rhIL-6 (10 microg/animal/d) subcutaneously also began to form bundles in proportion to an increase in platelet counts. After the administration of rhIL-6, about half of the megakaryocytes contained microtubule bundles in their cytoplasm. These results indicate that microtubule-bundle formation is one maturational event in megakaryocyte development and that rhIL-6 could accelerate this event.

Thrombopoietic effects of interleukin-6 in long-term administration in mice.

To further investigate the thrombopoietic and adverse effects of interleukin-6 (IL-6), 2 or 10 micrograms/day of recombinant human (rh) IL-6 was administered intraperitoneally (i.p.) to mice for up to 30 days. IL-6 increased platelet count, which plateaued at a level 30 to 40% higher than control after 5 days of treatment. This cytokine also maintained the high platelet count for the duration of treatment. The count exceeded normal levels 7 days after cessation of the 30-day treatment. IL-6 also induced a remarkable increase in the size but not the frequency of megakaryocytes in bone marrow sections. The number of bone marrow colony-forming units megakaryocyte (CFU-MK) and colony-forming units granulocyte-macrophage (CFU-GM) was not augmented by the administration of IL-6 in this protocol, while spleen progenitors were significantly stimulated. Small but significant increases did occur in the number of bone marrow megakaryocytes and CFU-MK, and in the proportion of CFU-MK in the DNA synthetic phase in mice treated with 10 micrograms/day of IL-6 for 30 days. Electron microscopic examination of bone marrow demonstrated that IL-6 remarkably developed the distribution of the demarcation membrane system (DMS) in mice treated for 30 days, with little change in mice treated for 5 days. The administration of 2 micrograms/day for 30 days induced a 2.2-fold increase in fibrinogen. No changes were observed in the hepatic or renal functions. Histologic and immunofluorescence studies on the kidneys revealed no significant changes compared with controls, indicating that proliferation of the glomerular mesangium did not occur. No neutralizing antibodies were detected in mice treated for 30 days. We conclude that the long-term administration of IL-6 in mice stimulates megakaryocyte maturation and platelet production with few adverse effects, and that this cytokine may be a candidate for the treatment of thrombocytopenia in humans.

Amyloid fibril protein in familial amyloid polyneuropathy.

Amyloid fibril protein was purified from organs of patients with familial amyloid polyneuropathy (Nagano prefecture, Japan). When compared with amyloid fibril protein from primary amyloidosis and secondary amyloidosis, the protein from familial amyloid polyneuropathy was shown to differ in the molecular weight of the subunit. This protein subunit had the same molecular weight as the prealbumin subunit, but had a different amino acid composition: It did not contain tryptophan and cysteine. Amyloid fibril protein from familial amyloid polyneuropathy therefore differed from IgG, AA protein, and prealbumin.

A new method of gene transfer into hematopoietic progenitors using liquid culture with interleukin-3 and interleukin-6.

The technique of gene transfer into hematopoietic cells is expected to offer a new form of therapeutics. As a result of studies on a gene-delivery system using granulocyte-macrophage colony-forming units (CFU-GM), a type of hematopoietic progenitor, we have established a technique for efficient gene transfer into CFU-GM. DGL, a retrovirus vector containing the SV40 promoter and the neomycin resistance gene, was constructed and found to transfer genes effectively into murine CFU-GM, which subsequently expressed the neomycin resistance gene. After gene transfer of murine non-adherent bone marrow cells precultured in liquid culture with recombinant murine IL-3 (rmIL-3) and recombinant human IL-6 (rhIL-6) for 6 days, gene transferred CFU-GM in bone marrow cells were able to proliferate 5-10-fold and the ratio of gene transferred CFU-GM to total CFU-GM reached 70-100% from less than 1% in the liquid culture with rmIL-3, rhIL-6 and neomycin for 6 days. Using this protocol, we have been able to obtain large amounts of highly concentrated gene-transferred CFU-GM for fundamental research on CFU-GM gene-delivery systems.

Autoantibodies to each protein fraction extracted from cerebral endothelial cell membrane in the sera of patients with multiple sclerosis.

Damage to the blood-brain barrier (BBB) occurs in multiple sclerosis (MS), probably due to an immunological mechanism. Anti-endothelial cell antibodies may play a pathogenetic role in the BBB damage. Our previous studies led us to search for which protein fraction extracted from cerebral endothelial cell membrane was reactive to antibodies in the sera of patients with MS. The antibodies to each protein fraction extracted from the rat cerebral endothelial cell membrane were studied in patients with MS, other neurological diseases and controls using an enzyme-linked immunosorbent assay (ELISA) method. The patients with active relapsing MS (P less than 0.01) displayed significantly higher levels of immunoglobulin G (IgG) binding to the endothelial cell membrane fraction than did the controls. The sera of the same patients (P less than 0.001) also showed significantly higher levels of antibodies to fraction I (8.0 kDa) than did the normal controls. The high levels of IgG binding to fraction II (11.0 kDa) and III (12.3 kDa) were significantly increased in the sera of patients with active relapsing MS compared to normal controls (P less than 0.01). The immune response to the protein fraction extracted from the cerebral endothelial cell membrane fraction may indicate a result of the BBB damage in the case of MS.

A synergistic increase in transplantable peripheral blood stem cells in mice by co-administration of recombinant human interleukin 6 and recombinant human granulocyte colony-stimulating factor.

We examined the effects of co-administration of recombinant human (rh) IL-6 (10 micrograms/day) and rh granulocyte colony-stimulating factor (G-CSF) (0.35 micrograms/day) on the number of peripheral blood cells and peripheral progenitor cells in mice. Among blood cells counts, only white blood cells were synergistically enhanced by co-administration of rhIL-6 and rhG-CSF. Moreover, it was found that co-administration of rhIL-6 and rhG-CSF also caused a marked synergistic increase in the number of peripheral blood progenitor cells. Namely, in combination with rhG-CSF, which alone induced a 170-fold increase in peripheral granulocyte-macrophage colony-forming units (CFU-GM) on day 14, rhIL-6 synergistically increased the number of CFU-GM to more than 1600-fold higher than the number in control mice. Administration of rhIL-6 alone induced a 46-fold increase in CFU-GM. Similar synergistic increases of other hematopoietic progenitors, such as colony-forming units in spleen and megakaryocyte colony-forming units in blood, were also observed in mice co-administered rhIL-6 and rhG-CSF. The survival rate of lethally irradiated recipient mice transplanted with mononuclear cells from 100 microliters of blood from mice administered rhIL-6 and/or rhG-CSF was examined. When mononuclear cells from mice co-administered rhIL-6 and rhG-CSF were injected, survival rate at day 100 was 92%. In contrast, recipient mice transplanted with mononuclear cells from mice administered either rhIL-6 or rhG-CSF alone showed a survival rate of 31% or 46%, respectively, although transplantation of mononuclear cells from control mice failed to rescue any lethally irradiated recipient mice. These results suggest that co-administration of rhIL-6 and rhG-CSF may be useful for peripheral blood stem cell transplantation.

In vitro expansion of the murine pluripotent hemopoietic stem cell population in response to interleukin 3 and interleukin 6. Application to bone marrow transplantation.

The synergistic action of interleukin 6 with interleukin 3 on the proliferation of a murine hemopoietic stem cell population in a short-term liquid culture system was examined by radioprotective assay. The numbers of colony-forming units in spleen (CFU-S), together with granulocyte/macrophage colony-forming units and viable nucleated cells, were found to increase markedly in culture in the presence of both IL-3 and IL-6, compared with the presence of IL-3 or IL-6 alone. The peak CFU-S value in response to the combination of IL-3 and IL-6 was obtained 6 days after culture initiation, exceeding 5-fold of the input value. Consistent with these data, marrow cells cultured with both IL-3 and IL-6 for 6 days were shown to have a much higher capability of rescuing lethally irradiated mice than did controls. The results may portend the potential clinical use of the combination of IL-3 and IL-6, in particular, in bone marrow transplantation.

An increase in peripheral blood progenitor cells in primates by coadministration of recombinant human interleukin 6 and recombinant human granulocyte colony-stimulating factor.

BACKGROUND: We recently demonstrated that coadministration of recombinant human interleukin 6 (rhIL-6) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in mice synergistically increases peripheral blood stem cells (PBSC), which can rescue lethally irradiated recipient mice. However, there is little information about the effect of coadministration of rhIL-6 and rhG-CSF on PBSC in a primate system. METHODS: In cynomolgus monkeys, rhG-CSF (5 microg/kg day) alone was administered for 5 days (first cycle). After the wash-out period, rhIL-6 (0, 10, or 20 microg/kg/day) and rhG-CSF were coadministered for 5 days (second cycle). RESULTS: Total peripheral colony-forming cells levels were increased earlier by coadministration of rhIL-6 and rhG-CSF than by the administration of rhG-CSF alone. The maximum level in the coadministration cycle was obtained on day 5, and a high level was obtained for a further 3 days after cessation. The maximum number of peripheral total colony-forming cells in the coadministration cycle was a mean of 2.12-fold (range 1.38 to 3.35) higher than that in the rhG-CSF alone cycle. Coadministration also increased the peripheral mixed colony-forming units by a mean of 3.62-fold (range 1.02 to 5.52). Interestingly, monkeys that showed a low response to the administration of rhG-CSF alone also had a higher response to the coadministration. No significant difference was observed between the two cycles of administration of rhG-CSF alone. CONCLUSIONS: These findings suggest that coadministration of rhIL-6 and rhG-CSF may be useful for clinical PBSC collection.