Serum interleukin-17 & nitric oxide levels in patients with primary Sjögren's syndrome.

BACKGROUND & OBJECTIVES: The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO) as possible IL-17-induced product, in patients with primary Sjögren's syndrome (pSS), an intricate and complex chronic autoimmune disorder of exocrine glands. METHODS: Serum IL-17 levels and nitrite concentrations determined in patients with pSS (n=30) were compared with the values obtained in patients with RA (n=10) and healthy controls (n=15). The values obtained for IL-17 in pSS patients were also associated with the patients' clinical characteristics, particularly the rheumatoid factor (RF) and total antinuclear antibodies (tANA) levels. RESULTS: Serum concentrations of IL-17 were significantly (P<0.01) higher in patients with pSS (12.9 ± 28.0 pg/ml) as compared to those obtained in healthy individuals (0.2 ± 0.6 pg/ml), but not as high as the values obtained for the patients with RA (34.5 ± 56.2 pg/ml). The mean IL-17 levels were significantly (P<0.05) higher in the pSS patients positive for rheumatoid factor (20.3 ± 33.3 pg/ml) than in RF-negatives (0.3 ± 0.6 pg/ml). Mean serum concentrations of IL-17 were also higher in antinuclear antibody (ANA)-positive samples (19.8 ± 33.5 pg/ml) in comparison to ANA-negative sera (1.1 ± 3.1 pg/ml) (P<0.05). The NO levels also showed elevated values in both pSS and RA patients, as compared to the healthy controls, since mean nitrite levels in patients with pSS and RA were 38.2 ± 29.2 µM and 41.7 ± 21.1 µM, respectively, while those in healthy controls were significantly lower, at 19.2 ± 10.5 µM. INTERPRETATION & CONCLUSIONS: The findings of this study showed that there was increased IL-17 and NO production in patients with primary SS, especially if they had associated elevated rheumatoid factor and antinuclear antibody values.

Adolescent health in medieval Serbia: signs of infectious diseases and risk of trauma.

Although pattern of health in adults has been frequently assessed in past human populations, health status of adolescents as a distinct life stage has usually been overlooked. Inconsistency in number and meaning of recognised age categories in anthropological literature, as well as chronological age ranges used to define them, further complicate the interpretation of adolescent health. In this study, we analysed signs of pathological conditions on skeletal remains of 81 adolescents from a medieval site of Stara Torina (northern Serbia). Diagnostic palaeopathological procedures comprised gross examination, digital radiography, and histological analysis. Skeletal signs of anaemia such as cribra orbitalia and other porotic phenomena as well as signs of non-specific bone infection were observed frequently, while evidence of bone trauma was recorded in a very low percentage of individuals. In addition, we recorded two conditions relatively rarely observed in palaeopathological contexts: a case of skull and vertebral asymmetry indicative of congenital muscular torticollis, and a case of a fibrous cortical defect on distal femur. Comparison with available information from other medieval adolescent samples from Serbia demonstrated that while mortality was relatively constant throughout the sample, Stara Torina showed a much higher occurrence of bone disease. Characteristics of observed skeletal conditions, supported by available historical reports, suggest that the health of medieval adolescents in the examined population was most significantly affected by infectious processes.

Combined effect of IL-17 and blockade of nitric oxide biosynthesis on haematopoiesis in mice.

AIM: The study was undertaken to extend our investigation concerning both the in vivo activity of interleukin (IL)-17 and the specific role of nitric oxide (NO) in IL-17-induced effects in the process of haematopoiesis. METHODS: CBA mice were simultaneously treated with IL-17 and/or nitric oxide synthase (NOS) inhibitor, l-NAME, for 5 days and changes within various haematopoietic cell lineages in bone marrow, spleen and peripheral blood were analysed. RESULTS: Findings showed that administration of both IL-17 and l-NAME stimulated increase in net haematopoiesis in normal mice. IL-17-enhanced myelopoiesis was characterized by stimulation of both femoral and splenic haematopoietic progenitor cells and morphologically recognizable granulocytes. Additionally, IL-17 induced alterations in the frequency of erythroid progenitor cells in both bone marrow and spleen, accompanied with their mobilization to the peripheral blood. As a consequence of these changes in the erythroid cell compartments, significant reticulocytosis was observed, which evidenced that in IL-17-treated mice effective erythropoiesis occurred. Exposure of mice to NOS inhibitor also increased the number of both granulocyte-macrophage and erythroid progenitors in bone marrow and spleens, and these alterations were followed by the mobilization of erythroid progenitors and elevated content of reticulocytes in peripheral blood. The specific role of NO in IL-17-induced haematopoiesis was demonstrated only in the IL-17-reducing effect on bone marrow late stage erythroid progenitors, CFU-E. CONCLUSION: The results demonstrated the involvement of both IL-17 and NO in the regulation of haematopoietic cell activity in various haematopoietic compartments. They further suggest that IL-17 effects are differentially mediated depending on the haematopoietic microenvironments.

Burnout in Belgrade orthopaedic surgeons and general practitioners, a preliminary report.

BACKGROUND: Burnout syndrome (BOS) is caused both by psychological-emotional and physical stress. It is associated with decreased job performance and low career satisfaction. BOS has a significance influence both to physicians' performance in health care system, and in their private life. Until now, there was no data about this aspect of orthopaedic surgeon condition and health in our community. AIM: To assess the level of the burnout syndrome in orthopaedic surgeons and general practitioners (GPs), and the relations of their demographic features, job characteristics to the burnout syndrome DESIGN: Questionnaire-based survey METHODS: The sample consisted of 30 orthopaedic surgeons from the University Clinical Centre, and 40 GPs from the primary health care centres. The Burnout syndrome was measured by the Maslach Burnout Inventory (MBI). In addition to the MBI, the demographic data were collected and analyzed (age, age of practicing, gender, marital status) in relation to BOS. RESULTS: Both groups expressed moderate to high rate of emotional exhaustion, depersonalization and low personal accomplishment. However, statistical significance between the groups had not been demonstrated. Neither gender nor years of practice or marital status did express statistically significant impact on the BOS items, i.e. they were not predictors of the BOS. Our results showed that about 70% of the physicians were emotionally exhausted considering both groups. On the other hand, orthopaedics demonstrated slightly higher depersonalisation level (55%) than GPs (38%). While GPs expressed lower personal accomplishment (48%) comparing to orthopaedics (29%). DISCUSSION: The obtained MBI scores in this study were similar to those registered in US among residents, but when comparing to physicians in West Europe, which have similar health care system, our results demonstrated higher rates of BOS items. CONCLUSION: The Burnout syndrome represents an important problem for actively practicing physicians. The results of this and other similar studies should be used to evaluate medical training, practice, professional relations and introduce necessary changes.

The effect of interleukin-17 on hematopoietic cells and cytokine release in mouse spleen.

To evaluate whether the response of hematopoietic cells to interleukin-17 (IL-17) depends on the tissue microenvironment in which hematopoiesis occurs, the influence of recombinant mouse IL-17 on spleen hematopoietic cells and cytokine release was assessed in normal mice in vitro and in vivo. In vitro, IL-17 did not significantly affect the growth of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E and CFU-E) derived colonies. A single injection of IL-17 in vivo exhibited stimulatory effects on hematopoietic cells from both granulocytic and erythroid lineages. The increased number of metamyelocytes 48 h after treatment imply to the IL-17-induced stimulation of granulopoiesis. The number of BFU-E was increased at 24 h, while the number of CFU-E increased 6 h and 24 h after treatment. Since the same treatment in the bone marrow decreased the number of CFU-E, it may be concluded that the local microenvironment plays an important role in IL-17-mediated effects on CFU-E. IL-17 increased the release of IL-6 both in vitro and in vivo, but showed tendency to suppress the constitutive secretion of IL-10 by spleen cells. Our results suggest the complexity of target cell response and interplay of secondary induced cytokines by IL-17 in different hematopoietic organs.

In vivo effects of interleukin-17 on haematopoietic cells and cytokine release in normal mice.

In order to gain more insight into mechanisms operating on the haematopoietic activity of the T-cell-derived cytokine, interleukin-17 (IL-17) and target cells that first respond to its action in vivo, the influence of a single intravenous injection of recombinant mouse IL-17 on bone marrow progenitors, further morphologically recognizable cells and peripheral blood cells was assessed in normal mice up to 72 h after treatment. Simultaneously, the release of IL-6, IL-10, IGF-I, IFN-gamma and NO by bone marrow cells was determined. Results showed that, in bone marrow, IL-17 did not affect granulocyte-macrophage (CFU-GM) progenitors, but induced a persistant increase in the number of morphologically recognizable proliferative granulocytes (PG) up to 48 h after treatment. The number of immature erythroid (BFU-E) progenitors was increased at 48 h, while the number of mature erythroid (CFU-E) progenitors was decreased up to 48 h. In peripheral blood, white blood cells were increased 6 h after treatment, mainly because of the increase in the number of lymphocytes. IL-17 also increased IL-6 release and NO production 6 h after administration. Additional in vitro assessment on bone marrow highly enriched Lin- progenitor cells, demonstrated a slightly enhancing effect of IL-17 on CFU-GM and no influence on BFU-E, suggesting the importance of bone marrow accessory cells and secondary induced cytokines for IL-17 mediated effects on progenitor cells. Taken together, these results demonstrate that in vivo IL-17 affects both granulocytic and erythroid lineages, with more mature haematopoietic progenitors responding first to its action. The opposite effects exerted on PG and CFU-E found at the same time indicate that IL-17, as a component of a regulatory network, is able to intervene in mechanisms that shift haematopoiesis from the erythroid to the granulocytic lineage.

In vitro sensitivity of hematopoietic progenitors to tiazofurin in refractory acute myeloid leukemia and in the blast crisis of chronic myeloid leukemia.

The effect of Tiazofurin (TR) on the in vitro growth of bone marrow (BM) and peripheral blood (PB) leukemic progenitors was investigated in 29 patients. Nineteen of the patients were suffering the blast crisis of chronic myeloid leukemia (bcCML) and ten patients refractory acute myeloid leukemia (AML). PB and BM mononuclear cells were cultured in methylcellulose alone or with concentrations of TR ranging between 10 and 200 microM. TR produced a dose dependent inhibition of colony forming unit (CFU)-blast growth in all the samples tested from BM and PB. The most effective concentrations of TR used were 150 and 200 microM, while concentrations of less than 50 microM TR were not adequate for 50% inhibition of cell growth (IC50). Differences were found in the response of CFU-blasts to TR related to the type of underlying leukemia. Inhibition of CFU-blast growth was more pronounced in bcCML than in AML in both the BM and PB samples. The concentration of TR required to induce IC50 in bcCML was 50 microM, while the same effect in AML required a concentration of 150 microM. Analysis of the control samples also revealed that CFU-blasts from bcCML produced smaller numbers of colonies, though these differences were not statistically significant. It has therefore been demonstrated that TR has strong in vitro anti-leukemic activity, more pronounced in bcCML than in refractory AML. We thus feel this study gives further rationale for the clinical application of TR, and would strongly support this.

Effect of IL-17 on in vitro hematopoietic progenitor cells growth and cytokine release in normal and post-irradiated murine bone marrow.

The influence of recombinant human IL-17 on granulocyte-macrophage (CFU-GM) and erythroid (BFU-E and CFU-E) progenitors and the release of IL-1alpha/beta, IL-6 and erythropoietin (EPO) was estimated in the bone marrow cells obtained from normal and sublethally irradiated mice. In normal mice IL-17 increased CFU-GM and BFU-E and reduced CFU-E derived colonies numbers and augmented release of IL-6 and EPO. In irradiated mice the effects of IL-17 on hematopoietic progenitors were lineage-dependent, as well as dependent on their stage of differentiation and the time after the irradiation. IL-17 had no major effects on CFU-GM on day 1 and 3, but decreased their number on day 2, while enhanced both BFU-E and CFU-E on day 1 and 2 after irradiation, whereas on day 3 its effect on erythroid progenitors was again as observed in normal mice. After irradiation, IL-17 increased the release of IL-1alpha, IL-6 and EPO. The observed effects suggested the involvement of IL-17 in the regulation of hematopoiesis and indicated that its effects on both hematopoietic progenitors and cytokine release are dependent on the physiological/pathological status of the organism.

The Serbian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Serbian language of the parentís version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Serbian CHAQ-CHQ were fully validated with 3 forward and 1 backward translations. A total of 139 subjects were enrolled: 79 patients with JIA (30% systemic onset, 28% polyarticular onset, 6% extended oligoarticular subtype, and 36% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Serbian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Effects of treatment with interleukin-1 receptor antagonist on endogenous interleukin-1 levels in normal and irradiated mice.

The in vivo effects of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) administration on endogenous IL-1 levels in the circulation and conditioned media (CM) from different immunohematopoietic organ/tissues were studied in CBA mice under steady state and postirradiation conditions. In normal mice, constitutive IL-1 levels were demonstrated in the plasma, CM of peritoneal exudate cells and full-thickness skin explants with low or undetectable levels in CM of splenic and bone marrow cell suspensions. In irradiated mice (2 Gy, X rays) on day 3 post exposure a significant increase of IL-1 levels was seen in the circulation and CM of peritoneal exudate cells, with no significantly different levels in postirradiation bone marrow, spleen and skin. After rhIL-1Ra treatment of the animals (2 x 50 microg/mouse, i.p.), significantly elevated IL-1 levels were observed in the skin and CM of peritoneal exudate cells in normal mice, whereas slightly increased levels were detected in CM of splenic cells. The rhIL-1Ra administration in irradiated mice led to decreased IL-1 concentrations in the circulation, and CM of peritoneal exudate cells and skin. The results pointed out the importance of IL-1 secretion and receptor expression in the maintenance of homeostasis in steady state, as well as during recovery after irradiation. Modulatory effects of IL-1Ra on IL-1 production were dependent on basic endogenous IL-1 concentration.

Incubation of murine bone marrow cells in hypoxia ensures the maintenance of marrow-repopulating ability together with the expansion of committed progenitors.

We developed previously a hypoxic culture system in which progenitors endowed with marrow-repopulating ability (MRA), unlike committed progenitors, were selected and maintained better than in air. We report here an improvement to this system targeted at combining the maintenance of progenitors sustaining MRA with the numerical expansion of multipotent and committed progenitors. Murine bone marrow cells were incubated at 1% oxygen in liquid medium supplemented with stem cell factor, granulocyte colony-stimulating factor, interleukin-6 and interleukin-3. In day 8 hypoxic cultures, the numbers of high proliferative potential and granulocyte/macrophage colony-forming cells (HPP-CFC and CFU-GM) were increased with respect to time zero. Colonies generated by HPP-CFC derived from hypoxic cultures exhibited a high replating ability, whereas colonies generated by HPP-CFC derived from control cultures exhibited a low replating ability. MRA was fully maintained in hypoxia and markedly reduced in air. Thus, severe hypoxia is able to ensure a full maintenance of progenitors sustaining MRA, together with a significant expansion of in vitro-detectable clonogenic progenitors, including those endowed with replating ability. This system could contribute to the improvement of current techniques for the in vitro treatment of human haematopoietic cell populations before transplantation.

Effects of nitric oxide donors on energy metabolism of rat erythrocytes.

It is known that nitric oxide (NO) influences the activities of glycolytic enzymes, resulting in alteration of glycolysis rate. We investigated the effect of NO donors on the energy metabolism of rat erythrocytes. Rat erythrocyterich blood suspensions were aerobically incubated for 2 hours (1) as controls or (2) with different concentrations of NO donors: nitroglycerin (NTG), isosorbide dinitrate (ISDN), molsidomine (MO), and sodium nitroprusside (SNP). NTG, ISDN, MO, and SNP significantly (p < 0.05) increased glucose consumption and lactate accumulation in rat erythrocytes in a dose-dependent manner, indicating stimulation of glycolysis. The increased rate of glycolysis was accompanied by elevation of energy production (p < 0.05), but no changes in ATP levels were observed. The dose-dependent increase of glycolytic ATP production and the unaltered levels of ATP resulted in considerably shortened ATP-turnover time with the maximal experimental doses of NO donors used, indicating the stimulation of the ATP-consuming process in rat erythrocytes. The metabolic effects of NTG, ISDN, MO, and SNP were not mimicked by exogenous 8-Br-cGMP, NaNO2, or NaNO3, suggesting that the NO donor-induced stimulation of glycolysis and abbreviation of ATP-turnover time in rat erythrocytes was mediated by NO as an effector molecule, irrespective of the irreversible scavenger effect of hemoglobin. The implications of the NO effect on energy metabolism of erythrocytes is discussed.

A simple, one-step clonal assay allows the sequential detection of committed (CFU-GM-like) progenitors and several subsets of primitive (HPP-CFC) murine progenitors.

Murine bone marrow (BM) cells were cultured in semisolid medium containing interleukin 3 (IL-3) and high doses of G-CSF. Colonies were counted twice, at day 7 and day 14, and the number of granulocyte/macrophage colony-forming units (CFU-GM) accurately estimated by the subtraction of day-14 from day-7 colonies, based on the principle that colonies detectable at day 7 and persisting beyond day 14 are generated by significantly more immature progenitors. The frequency of colonies relative to their size was determined and used to define subsets of high proliferative potential colony-forming cells (HPP-CFC). Two main groups of HPP-CFC were considered: those generating colonies of 0.6-1.8 mm of diameter or larger than 1.8 mm. The characterization of these groups showed that they correspond to different functional subsets of HPP-CFC. The replating ability of colonies was estimated. The percentage of clonogenic progenitors in the S phase of cell cycle was measured by cytosine arabinoside suicide assay. The sensitivity of colonies to 5-fluorouracil (5-FU) in vitro was determined and their survival after an in vivo treatment with 5-FU compared with that of colony-forming units in spleen (CFU-S). This technique allowed identification of: A) CFU-GM; B) relatively mature HPP-CFC, probably corresponding to CFU-S day12; C) more primitive HPP-CFC, relatively resistant to 5-FU in vivo and closely corresponding to CFU-S day 14, and D) very primitive HPP-CFC, resistant to 5-FU in vitro. This simple, rapid, and versatile method allows the detection of a broad range of hematopoietic progenitors in murine BM, from committed progenitors to largely quiescent, primitive stem cells, as well as the evaluation of the progenitors' self-renewal and proliferative potential.

The cryopreservation protocol optimal for progenitor recovery is not optimal for preservation of marrow repopulating ability.

The efficiency of five different cryopreservation protocols (our original controlled-rate and noncontrolled-rate protocols) was evaluated on the basis of the recovery after thawing of very primitive pluripotent hemopoietic stem cells (MRA(CFU-GM), pluripotent progenitors (CFU-Sd12) and committed granulocyte-monocyte progenitors (CFU-GM) in mouse bone marrow. Although the nucleated cell recovery and viability determined immediately after the thawing and washing of the cells were found to be similar, whether controlled-rate or noncontrolled-rate cryopreservation protocols were used, the recovery of MRA(CFU-GM), CFU-Sd12 and CFU-GM varied depending on the type of protocol and the cryoprotector (DMSO) concentrations used. It was shown that the controlled-rate protocol was more efficient, enabling better MRA(CFU-GM), CFU-Sd12 and CFU-GM recovery from frozen samples. The most efficient was the controlled-rate protocol of cryopreservation designed to compensate for the release of fusion heat, which enabled a better survival of CFU-Sd12 and CFU-GM when combined with a lower (5%) DMSO concentration. On the contrary, a satisfactory survival rate of very primitive stem cells (MRA(CFU-GM)) was achieved only when 10% DMSO was included with a five-step protocol of cryopreservation. These results point to adequately used controlled-rate freezing as essential for a highly efficient cryopreservation of some of the categories of hematopoietic stem and progenitor cells. At the same time, it was obvious that a higher DMSO concentration was necessary for the cryopreservation of very primitive stem cells, but not, however, for more mature progenitor cells (CFU-S, CFU-GM). These results imply the existence of a mechanism that decreases the intracellular concentration of DMSO in primitive MRA cells, which is not the case for less primitive progenitors.

Pluripotent haemopoietic progenitor cells (CFU-Sd8) in peripheral blood of hereditarily anaemic Belgrade (b/b) rats.

The unique anaemic syndrome of the Belgrade laboratory (b/b) rat is due to an intracellular iron deficiency which is induced by a not yet defined mutation, resulting in impairment of haemopoiesis. We investigated the CFU-Sd8 number and concentration in the peripheral blood of b/b rats to study the relationship between medullary and extramedullary haemopoiesis in this anaemic syndrome. The results show normal concentration of CFU-Sd8 in the peripheral blood of b/b rats. This finding was unexpected in the state of severe anaemia and disturbed growth factor production in b/b rats, where the mobilization of CFU-Sd8 from bone marrow to blood is expected. The results suggest that severe anaemia is not regularly accompanied by the mobilization of pluripotent progenitors from bone marrow to the blood.

Alpha- and beta-globins of the anemic Belgrade laboratory rat. II. The effect of hemin and iron-dextran treatment.

We have studied the changes in bone marrow and spleen globin chain levels after in vivo hemin and iron-dextran treatment of hereditarily anemic Belgrade laboratory (b/b) rats. The increase of globin chains was detected in the bone marrow and in the spleen when b/b animals were treated with either iron or hemin. The analysis of changes in alpha- and beta-globin chain ratios revealed the distinctive role of these molecules in regulating globin chain status. Iron-dextran, as expected, ameliorated the imbalance of alpha- and beta-globin chains in the b/b rat spleen. On the other hand, hemin, as we have hypothesized in the accompanying paper, leads to a surplus of beta-globin chains in the bone marrow, similar to the one detected in the b/b rat spleen. Therefore, an iron-rich microenvironment has a stimulatory effect, while a hemin-rich microenvironment has an inhibitory effect on erythropoiesis.

The inhibitory effect of human macrophage inflammatory protein-1 alpha (LD78) on acute myeloid leukemia cells in vitro.

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has recently been shown to inhibit proliferation of immature hemopoietic progenitors. In addition, significant inhibition of early and mature leukemic progenitors in acute myeloid leukemia (AML) has been obtained with MIP-1 alpha. We performed a study of 25 AML patients at diagnosis to evaluate the effect of a human homolog of MIP-1 alpha (LD78) on bone marrow (BM) and peripheral blood (PB) leukemic progenitors (colony-forming unit-AML [CFU-AML]) and AML cell proliferation. A methylcellulose culture system was used for CFU-AML and incorporation of 3H-TdR for AML cell proliferation. We found that LD78 inhibits CFU-AML colony formation up to 100% for the BM in 14/16 samples studied with the average maximal inhibition of 62.7 +/- 9.1% and up to 100% for the PB in 12/13 samples studied with the average maximal inhibition of 71.4 +/- 9.9%. In addition to this, LD78 inhibited AML cell proliferation up to 60% for the BM in 10/18 samples studied with the average maximal inhibition of 17.8 +/- 3.5%, and up to 87.1% for the PB cell proliferation in 10/16 samples studied with the average maximal inhibition of 27.5 +/- 6.8%. Our results have shown that LD78 is more active on AML progenitors than on AML cell proliferation. Inhibition of the AML cells, although less than that of the progenitors, indicates that more limited activity of LD78 on more mature leukemic cells is present in AML.

The effect of IL-1 receptor antagonist on the proliferation of hematopoietic progenitor cells in regenerating bone marrow.

To evaluate the involvement of IL-1 on bone marrow granulocyte-macrophage (CFU-GM) and erythroid (BFU-E and CFU-E) progenitor cell regeneration during the recovery of hematopoiesis after sublethal irradiation of CBA mice, we examined the effects of IL-1 receptor blockade by recombinant human IL-1 receptor antagonist (rhIL-1ra). The actual number of progenitors and proportion of these cells in S phase of the cell cycle were determined in regenerating bone marrow cells obtained 3 days after 2 Gy irradiation both following the in vivo administration of rhIL-1ra, as well as after the in vitro preincubation with increasing amounts of rhIL-1ra. The results revealed that rhIL-1ra decreased the number and the proportion of CFU-GM in the S phase in regenerating bone marrow. As concerning erythroid progenitors, rhIL-1ra treatment suppressed BFU-E and enhanced CFU-E-derived colony growth, indicating that the biological effects of IL-1 might be different depending on the stage of differentiation. The observed effects pointed to the importance of the basal levels of IL-1, as well as IL-1 receptor expression during the recovery of hematopoiesis.