The Effect of Ibuprofen on Cytokine Production by Mononuclear Cells from Schizophrenic Patients.

The existence of a restrained inflammatory state in schizophrenic individuals posed the question whether anti-inflammatory drugs may exert antipsychotic effects. Therefore, the effect of ibuprofen (IB) on cytokine production by human peripheral blood mononuclear cells (PBMC) from schizophrenic patients was examined and compared to that of healthy subjects. PBMC from 25 schizophrenic patients and 24 healthy volunteers were incubated for 24 h with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IB. The levels of IL-1ß, IL-6, TNF-α, IL-10 and IL-1ra in the supernatants were tested applying ELISA kits. The secretion of TNF-α by cells from schizophrenic patients was significantly lower compared with controls. IB caused stimulation of TNF-α and IL-6 production by cells of the two groups and enhanced IL-1ß secretion by cells from schizophrenic patients. IB inhibited IL-1ra and IL-10 generation by cells from the two groups. Without IB, IL-1ra secretion was negatively correlated with the disease severity, while 200 µg/ml of IB positively correlated with the PANSS total score. IL-10 production was positively correlated with the PANSS positive subscale score both in the absence or presence of IB. The findings suggest that the effect of IB on the production of inflammatory cytokines may benefit the health of schizophrenic patients.

Vitamin B6 Modifies the Immune Cross-Talk between Mononuclear and Colon Carcinoma Cells.

The role of vitamin B6 as a key component in a number of biological events has been well established. Based on the relationship between chronic inflammation and carcinogenesis on the one hand, and the interaction between immune and cancer cells expressed by modulated cytokine production on the other hand, the aim of the present work was to examine the possibility that vitamin B6 affects cancer development by an interference in the cross-talk between human peripheral blood mononuclear cells (PBMC) and those from two colon carcinoma cell lines. Both non-stimulated PBMC and mononuclear cells induced for cytokine production by HT-29 and RKO cells from human colon carcinoma lines were incubated without and with 4, 20 and 100 µg/ml of pyridoxal hydrochloride (vitamin B6) and secretion of TNF-α, IL-1ß, IL-6, IFN-γ, IL-10, and IL-1ra was examined. Vit B6 caused a dose-dependent decrease in production of all cytokines examined, except for that of IL-1ra. The results indicate that vitamin B6 exerts an immunomodulatory effect on human PBMC. The finding that production of inflammatory cytokines is more pronounced when PBMC are in contact with malignant cells and markedly inhibited by the vitamin suggests an additional way by which vitamin B6 may exert its carcinopreventive effect.

Difference in inflammatory cytokine production by mononuclear cells from obese and non-obese schizophrenic patients.

OBJECTIVE: Schizophrenic patients have an increased risk for obesity compared with the general population. Evidence suggests the existence of an inflammatory process in the etiology of both obesity and schizophrenia. Our study compares in vitro secretion of inflammatory cytokines by peripheral blood mononuclear cells (PBMC) obtained from obese and non-obese schizophrenic patients. METHOD: Mononuclear cells were isolated from 20 obese (BMI >27) and 20 non-obese (BMI <24) schizophrenic in-patients. The levels of TNF-α, IL-1ß, IL-6, IL-1ra, IL-10 or IL-2 and IFN-γ in the supernatants of stimulated PBMC, as well as leptin and adiponectin serum values were evaluated. RESULTS: Peripheral blood mononuclear cells from patients in the obese group showed a significantly increased TNF-α and IL-1ß production, whereas the release of IL-1ra was decreased as compared with the non-obese group. In the obese group, the serum concentration of leptin was significantly higher and that of adiponectin was significantly lower. The results of the remaining cytokines did not differ between the two groups. CONCLUSION: Our study indicates the existence of a difference between obese and non-obese schizophrenic subjects as for inflammatory cytokine production and serum leptin and adiponectin levels, suggesting a 'subclinical inflammatory state' in obese schizophrenic patients that may contribute to a predisposition to inflammation and infections.

Effects of prolonged in vitro culture and cryopreservation on viability, DNA fragmentation, chromosome stability and ultrastructure of bovine cells from amniotic fluid and umbilical cord.

The objective of this work was to study cellular types that did not participated in the gastrulation process, amniotic fluid cells (AFCs) and umbilical cord cells (UCCs), in conditions of long-term culture and cryopreserved with different solutions. The AFCs and UCCs were used in a comparative study with ear fibroblast cells (EFCs) that were cultured in vitro until 20 cellular passages and cryopreserved in 10% dimethylsulphoxide (DMSO), 5% dimethyl formamide (DMF) and 7% glycerol (Gly) solutions. The cellular viability, ultrastructure, DNA fragmentation and chromosome stability were evaluated to determine the cellular type most resistant. In all cell types, it was possible to evaluate the AFCs until 15 passages and UCCs until 20 passages with different periods of cellular growth to reach the confluence phase. Solutions containing 10% DMSO ensured viability of 90.33 ± 5.58%, 90.56 ± 4.40% and 81.90 ± 3.31%, respectively for EFCs, AFCs and UCCs, being significantly more efficient and with less variation than other cryoprotectant solutions. The AFCs were more sensitive to cryopreservation and presented low viability rate at the passage 20 (17.2 ± 8.87%). There was no change in karyotype and nuclear fragmentation was low in all cellular passages studied. With the scanning electron analysis was possible the characterization of AFCs and UCCs in suspension. The three cellular types of cells presented different shapes and characteristics on the surface. The results demonstrate that bovine AFCs and UCCs can be isolated, cultured in vitro and cryopreserved in 10% DMSO, not causing damage to DNA and chromosomes. The UCCs were more resistant than AFCs in all aspects.

Plant diversity effects on soil microorganisms support the singular hypothesis.

The global decline in biodiversity has generated concern over the consequences for ecosystem functioning and services. Although ecosystem functions driven by soil microorganisms such as plant productivity, decomposition, and nutrient cycling are of particular importance, interrelationships between plant diversity and soil microorganisms are poorly understood. We analyzed the response of soil microorganisms to variations in plant species richness (1-60) and plant functional group richness (1-4) in an experimental grassland system over a period of six years. Major abiotic and biotic factors were considered for exploring the mechanisms responsible for diversity effects. Further, microbial growth characteristics were assessed following the addition of macronutrients. Effects of plant diversity on soil microorganisms were most pronounced in the most diverse plant communities though differences only became established after a time lag of four years. Differences in microbial growth characteristics indicate successional changes from a disturbed (zymogeneous) to an established (autochthonous) microbial community four years after establishment of the experiment. Supporting the singular hypothesis for plant diversity, the results suggest that plant species are unique, each contributing to the functioning of the belowground system. The results reinforce the need for long-term biodiversity experiments to fully appreciate consequences of current biodiversity loss for ecosystem functioning.

Effect of citrus pectin on malignant cell proliferation.

The effect of citrus pectin (CP) on the proliferative capacity of four malignant cell lines was examined. Various dose of CP inhibited the proliferation of two-colon carcinoma and an erythroleukemia cell lines. Raji cells were not affected at all. The three lines affected by CP are known to express galectins which are pivotal for cell growth and metastasis, while Raji cells, whose proliferation was not affected by CP, are deficient of this betagalactoside. It is possible that the antiproliferative effect of CP on the malignant cells may be due at least in part to its ability to inhibit galectin expression.

Immune response to influenza and pneumococcal vaccines in mice.

The immune response of mice injected with influenza vaccine (FluV) or pneumococcal vaccine (PV) given separately or simultaneously was evaluated. Balb/c mice were divided into six groups. Group I served as control, the mice in group II were injected intraperitoneally with PV, in group III intramuscularly with FluV two weeks after the onset of the study. The mice from group IV received PV and 2 weeks later were injected with FluV, mice in group V were given FluV, whereas group VI received both FluV and PV simultaneously. The results showed that the proliferative response of peripheral blood mononuclear cells (PBMC) significantly increased in animals from groups II, V and VI, whereas the proliferation of splenocytes increased in mice from groups II, III, IV, and VI. These observations indicate a comparable effect of both vaccines, at least when the proliferative response of PBMC and splenocytes were considered.

Low-dose ketamine affects immune responses in humans during the early postoperative period.

BACKGROUND: Anaesthesia and surgery are associated with impairment of the immune system expressed as an excessive proinflammatory immune response and suppression of cell-mediated immunity that may affect the course of the postoperative period. Addition of anaesthetic agents capable of attenuating the alterations in perioperative immune function may exert a favourable effect on patients' healing. We have assessed the effect of preoperative administration of a sub-anaesthetic dose of ketamine on the mitogen response and production of interleukin (IL)-1beta, IL-2, IL-6, and tumour necrosis factor (TNF)-alpha by peripheral blood mononuclear cells (PBMCs), as well as natural killer cell cytotoxicity (NKCC) in patients undergoing abdominal surgery. METHODS: Seventeen patients admitted for elective abdominal surgery were given ketamine 0.15 mg kg(-1) i.v. 5 min before induction of general anaesthesia. Nineteen patients received a similar volume of isotonic saline 5 min before induction of the anaesthesia. PBMCs were isolated from venous blood before and 4, 24, 48, and 72 h after operation for IL-1beta, IL-2, IL-6, and TNF-alpha secretion, and NKCC assessment. RESULTS: Four hours after operation, the cells from patients in the ketamine group showed a significantly suppressed production of IL-6 (P < 0.01) compared with controls. The production of IL-2 did not change from that of the preoperation samples. TNF-alpha secretion was significantly elevated in the control group 4 h after operation (P < 0.05). CONCLUSIONS: Addition of small doses of ketamine before induction of anaesthesia resulted in attenuation of secretion of the proinflammatory cytokines IL-6 and TNF-alpha, and in preservation of IL-2 production at its preoperative level. It is suggested that this anaesthetic may be of value in preventing immune function alterations in the early postoperative period.

Lycopene affects proliferation and apoptosis of four malignant cell lines.

The beneficial effect of lycopene from tomatoes on a variety of chronic diseases and particularly its association with decreased incidence of prostate and breast cancer seems to be well established. The aim of the study was to examine its anti-proliferative and apoptotic effect on other malignant cell lines. Cells of the following lines were incubated with 1.0, 2.0, and 4.0microM of lycopene: human colon carcinoma (HuCC), B chronic lymphocytic leukemia (EHEB), human erythroleukemia (K562) and Raji, a prototype of Burkitt lymphoma cell line. The results showed that lycopene exerted a significant dose-dependent effect on the proliferation capacity of K562, Raji and HuCC lines, whereas this effect was observed in EHEB cells only with the highest dose used in the study. Increased apoptotic rate was found after incubation of HuCC cells with 2.0 and 4.0microM of lycopene and in Raji cells following incubation with 2.0microM. The findings point out that the anti-proliferative effect of lycopene on tumor cells and its effect on the apoptotic rate depends on its dosage and on the type of the malignant cells.

A comparison of the effect of vitamin A on cytokine secretion by mononuclear cells of preterm newborns and adults.

BACKGROUND: For a long time vitamin A has been known to be essential for immune defense of the organism and protection against infections. Vitamin A deficiency in children is associated with morbidity and mortality from infectious diseases which could be prevented and even alleviated by vitamin A supplementation. Moreover, this vitamin is involved in the modulation of immunological and inflammatory responses by regulation of cytokine production. The aim of the study was to compare the in vitro effect of vitamin A on the production of pro-inflammatory (IL-1beta and IL-6) and anti-inflammatory (IL-1 receptor antagonist (ra) and IL-10) cytokines, as well as IL-2 and IFNgamma by cord blood mononuclear cells (CBMC) of preterm newborns to that of peripheral blood mononuclear cells (PBMC) from adults. METHODS: Mononuclear cells (MC) from individuals of the two age groups were incubated with vitamin A (retinyl palmitate) at various concentrations in the presence of phytohemagglutinin for IL-2 and IFNgamma production or LPS for IL-1beta, IL-1ra, IL-6 and IL-10 secretion. The level of the cytokines in the supernatants was tested by ELISA. RESULTS: Vitamin A exerted an in vitro inhibitory effect on the production of the anti-inflammatory cytokine IL-1ra by MC of preterm newborns and adults, but did not affect the secretion of the pro-inflammatory cytokines IL-1beta, IL-6 and IFNgamma. Vitamin A caused inhibition of IL-10 secretion by cells from adults, but it did not significantly affect this function in cells from newborns except when high unphysiological doses were applied. In addition vitamin A stimulated the secretion of IL-2 by cells isolated from adults but had no effect on those derived from premature neonates. CONCLUSIONS: The results indicate that vitamin A may affect the immune function of premature infants via inhibition of IL-1ra secretion. It is suggested that the beneficial effect of vitamin A on the clinical course of bronchopulmonary dysplasia (BPD) may be due to the reduced production of anti-inflammatory cytokines by neonatal CBMC. This may indicate the importance of the pro-inflammatory cytokines in the management of severe lung diseases and BPD.

Does pneumococcal vaccine reduce influenza morbidity in humans?

A retrospective study was conducted to verify the possibility that people immunized with pneumococcal vaccine (PV) show lower morbidity not only for pneumonia but also for influenza. A total of 450 individuals were enrolled between 1999 and 2003 and allocated to one of the following groups: (A) not vaccinated; (B) immunized with PV during 1999; (C) immunized with anti-influenza vaccine (Flu-V) each year; and (D) immunized with PV once in 1999 and Flu-V every consecutive year. People from group B showed significantly lower percentage of influenza-related diseases during the year 2000 in comparison with those from group A (p<0.01), whereas in the course of 2001 the morbidity of patients from group B was lower compared with the other groups (p<0.01). The results point to a way to decrease the morbidity of influenza-related diseases by immunization with PV only, at least for 2-3 years, avoiding Flu-V administration and permitting considerable saving for health care providers. Therefore, it is concluded that PV can reduce the morbidity of influenza at a greater rate than the Flu-V.

Anesthesiologists at work: an increase in pro-inflammatory and Th2 cytokine production, and alterations in proliferative immune responses.

BACKGROUND: Anesthesiologists are a population at high risk of alcohol and drug abuse, depression, suicide, and psychiatric hospitalization. The impact of their working milieu on specific immune indices has scarcely been studied, and it is assumed that immune perturbations may contribute to some of the above risks. This study took advantage of an unplanned, 3-month long strike of anesthesiologists, and explored its relations to specific immune measures. METHODS: We assessed induced cytokine production and lymphocytes proliferative responses in blood samples taken from 10 anesthesiologists just before the strike and at its end, after a long period of markedly reduced workload. RESULTS: The results indicated that the proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly lower at the end of the strike. At this time point, we observed a significant decrease in the production of interleukin-6 (IL-6), IL-10 and IL1ra levels, and a significant increase in IL-2 production. A strong trend towards a decline in tumor necrosis factor-alpha (TNF-alpha) levels was evident, while levels of IL-1beta were unchanged. CONCLUSION: These findings suggest that the working conditions of anesthesiologists are associated with specific immune alterations, including a shift towards a Th2 cytokines' dominance, and an elevated pro-inflammatory cytokine response. A reduced Th1 profile has been related to increased susceptibility to infections, and high pro-inflammatory cytokine levels were recently proposed as etiological factors in cardiovascular diseases and in depression.

Postoperative pain, morphine consumption, and genetic polymorphism of IL-1beta and IL-1 receptor antagonist.

Interleukin-1 beta (IL-1beta) and its endogenous IL-1 receptor antagonist (IL-1Ra) play an important role in inflammatory response and in pain modulation. It has recently been shown that polymorphism of the IL-1beta and IL-1Ra genes may account for variation in the production of these cytokines. The present study examined the hypothesis that polymorphism of IL-1beta and IL-1Ra genes is involved in pain sensitivity and morphine consumption in the immediate postoperative period. Genetic polymorphism was determined in 76 women undergoing transabdominal hysterectomy. The genotype of IL-1Ra was determined using PCR amplification of the variable number of tandem repeats (VNTR) of 86 base pair (bp) in intron 2, while for IL-1beta the cytosine to thymine transition at codon -511 of the promoter was determined by PCR. Morphine consumption and pain scores were evaluated in the first postoperative 24 h. The study group was divided based on morphine consumption to three sub-groups: low morphine consumers (LMC) (<28 mg/24 h), medium morphine consumers (MMC) (28-38 mg/24 h), and high morphine consumers (HMC) (>38 mg/24 h). Patients consuming the least amount of morphine postoperatively showed significant lower pain scores. IL-1Ra genetic polymorphism of the MMC group was significantly different compared to the other two groups. No difference in IL-1beta gene polymorphism was found among the three sub-groups. Since IL-1Ra polymorphism is known to affect the levels of both IL-1Ra and IL-1, cytokines associated with modulation of pain sensitivity and morphine analgesia, it is suggested that IL-1Ra genetic polymorphism may contribute to the variation in postoperative morphine consumption.

Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period.

BACKGROUND: Recently, new drugs and techniques for the treatment of postoperative pain were introduced, with the goal of enhancing opiates' analgesia while minimizing their side-effects. Cholinergic agents play an antinociceptive role, but their clinical use is quite limited, due to side-effects. Physostigmine is a cholinesterase inhibitor, which crosses the blood-brain barrier and elevates brain acetylcholine level. Physostigmine can produce analgesia by itself, and enhance opiate analgesia; but these effects are of short duration following bolus administration. METHODS: We compared pain intensity and morphine consumption in two postoperative treatment groups: One group received continuous physostigmine infusion combined with morphine-based patient-controlled analgesia (PCA), and the other received PCA alone. Cholinergic anti-inflammatory pathways have recently been described. We therefore also compared changes in proinflammatory cytokine production in the two pain management groups. RESULTS: Continuous infusion of physostigmine combined with morphine-based PCA in the postoperative period significantly reduced opiate consumption, and enhanced the analgesic response. Patients in the physostigmine group also exhibited reduced ex-vivo production of the proinflammatory cytokine, IL-1beta. At the same time, physostigmine increased nausea and vomiting, mostly in the first 2 h of the postoperative period. CONCLUSIONS: Physostigmine combined with morphine in the postoperative period reduced morphine consumption, enhanced analgesia, and attenuated production of the proinflammatory cytokine, IL-1beta. This latter finding may account for the decreased pain observed in this group; this cytokine is known to mediate basal pain sensitivity and induce hyperalgesia in inflammatory conditions. Taking into account the other potential beneficial effects of physostigmine, we suggest that a continuous infusion of physostigmine should be considered as a useful component in multimodal postoperative analgesia.

Association between IL-1ra gene polymorphism and premature delivery.

IL-1 receptor antagonist (IL-1ra) gene polymorphism was examined in 95 Israeli preterm newborns and compared to that of adult volunteers. The genotype was determined using PCR amplification of the variable region of intron 2 of the IL-1ra gene. The IL-1raA1 allele was found to be predominant in the two groups. However, a significant higher frequency of IL-1raA2 allele was found in preterm newborns. The difference was mainly due to higher proportion of homozygous for IL-1raA2 in the preterm neonates (19%) as compared with adults (7%). No such association could be demonstrated between IL-1raA2 allele and severe sepsis in preterm newborns. The frequency of IL-1raA2 allele among preterms with a septic episode did not differ significantly from that found in newborns without sepsis. The results suggest an association between the IL-1ra genotype and the incidence of premature delivery.

Pure red cell aplasia--a rare disease with multiple causes.

Pure red cell aplasia (PRCA) is a relatively rare disease although multiple factors are implied in the pathogenesis of its development. A slow progressive normocytic-normochromic anemia and reticulocytopenia, without leukopenia and thrombocytopenia in a patient who, except pallor, does not show abnormal findings on physical examination, should arise the suspicion that he has PRCA. Search for underlying diseases or infections and intake of drugs may help for the establishment of the diagnosis of acquired PRCA. Lack of erythroblasts in the bone marrow with normal development of the other hemopoietic series, as well as high level of serum erythropoietin are important clues for the diagnosis. Elimination of potentially causative factors, administration of immunosuppressive agents and/or recombinant erythropoietin, preferably epoetin beta, may induce remission and complete recovery.

On the mechanism of post-splenectomy leukocytosis in mice.

BACKGROUND: Increased number of peripheral white blood cells (PWBCs) has been noted after removal of the spleen. DESIGN: To clarify the possible mechanisms by which splenectomy affects the PWBC number, the percentage of apoptotic PWBCs, the number and migration rate of peritoneal cells, as well as the 3H-TdR incorporation into PWBCs, were examined in splenectomized, sham-operated and control mice. In addition, the effect of control plasma injected to splenectomized animals on the number of PWBCs was examined. RESULTS: One and two months after splenectomy the PWBC counts significantly increased, whereas the percentage of apoptotic PWBCs and the number of cells in the peritoneal cavity decreased in comparison with that of the control and sham-operated mice. Seventeen days after injection of carboxy-fluorescein diacetate succinimidyl ester (CFSE)-labelled peritoneal cells into the peritoneal cavity of the animals, their number was significantly higher in the peripheral blood and lower in the peritoneal cavity of the splenectomized animals in comparison with that of the control and sham-operated mice. Injection of control plasma into the splenectomized mice prevented the development of postsplenectomy leukocytosis. Finally, 3H-TdR incorporation into nonstimulated and Con A stimulated PBMCs from the splenectomized mice was higher as compared with cells from the control and sham-operated mice. CONCLUSIONS: The results of the study present several mechanisms that may clarify the cause of postsplenectomy leukocytosis.

Relationship between temperature and apoptosis of human peripheral blood mononuclear cells.

To examine the effect of various incubation temperatures on the apoptotic death of human peripheral blood mononuclear cells (PBMC), we incubated cells at 37 degrees C, 22 degrees C, and 4 degrees C for 1 and 24 hours. In addition, cells incubated at 4 degrees C for 3, 6, and 9 hours were rewarmed to 37 degrees C until a total incubation time of 24 hours was reached. The percentage of apoptotic cells was detected by a flow cytometric assay using propidium iodide staining. Incubation of PBMC at the above-mentioned temperatures for 1 hour did not affect the percentage of apoptotic cells. However, incubation at 4 degrees C for 24 hours resulted in the lowest percentage of apoptotic cells compared to those incubated at 22 degrees C and 37 degrees C. Rewarming of the cells to 37 degrees C increased the percentage of apoptotic cells to a level similar to that of the controls (incubated at 37 degrees C). Because PBMC are closely involved in the normal function of the immune system, the results of the study should be considered in cases in which these cells are exposed to various thermal conditions.

Immune response in asymptomatic smokers.

BACKGROUND: It has been demonstrated that cigarette smoking affects the immune system. Impairment of alveolar mononuclear cell function, described previously, may contribute to the higher rate of postoperative respiratory infections. However, increased susceptibility of smokers to infections of other origin (e.g. wound-related) implies that tobacco effect is not restricted to the respiratory immune competent cells. The present study was designed to investigate the systemic effect of tobacco smoking as it exerted on blood-derived immune cells. We measured systemic cytotoxic activity of natural killer cells, production of pro- and anti-inflammatory cytokines by blood mononuclear cells and their proliferation in response to mitogens. To minimize the immunosuppressive effect of other smoke-related factors, the smokers with chronic obstructive pulmonary disease (COPD) were excluded from this study. METHODS: Peripheral blood mononuclear cells (PBMC) from 24 chronic asymptomatic smokers, and 28 controls, age and gender matched, were isolated and incubated in vitro with lipopolysaccharide (LPS) or phytohemagglutinin (PHA) to induce secretion of IL-1beta, IL-1ra, IL-6, IL-10, TNFalpha and IL-2, respectively, from mononuclear cells. The level of the cytokines in the supernatants was measured using ELISA kits. The proliferative response to the mitogens PHA and concanavalin A (ConA) was evaluated by 3H-thymidine incorporation and NK cell cytotoxicity by 51Cr release assay. RESULTS: Mononuclear cells from smokers showed increased production of the pro-inflammatory cytokines IL-1beta, IL-6 and TNFalpha and enhanced proliferative response to mitogens as compared to non-smoking population. The secretion of IL-2 and the anti-inflammatory cytokines IL-1ra and IL-10 was similar in both groups. NK cell cytotoxic activity was suppressed in the smokers. CONCLUSION: Cigarette smokers without chronic obstructive pulmonary disease (COPD) exhibit impaired NK cytotoxic activity in peripheral blood and unbalanced systemic production of pro- and anti-inflammatory cytokines. These changes may serve as predisposing factors for respiratory and systemic infections in the postoperative period and should alert an anesthetist during perioperative management.

Indomethacin and ibuprofen effect on IL-1ra production by mononuclear cells of preterm newborns and adults.

The in vitro effect of indomethacin (IM) and ibuprofen (IB) on the production of the interleukin-1 receptor antagonist (IL-1ra) by cord blood mononuclear cells (CBMC) from preterm newborns was compared to that of peripheral blood mononuclear cells (PBMC) from adults. Mononuclear cells (MC) were incubated with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IM and IB. The level of IL-1ra in the supernatants was tested by ELISA. The results showed a lower ability of MC from preterm newborns to produce IL-1ra as compared with adult cells, supporting the assumption of neonatal immune cell immaturity. IM at pharmacological concentrations caused inhibition of IL-1ra secretion by PBMC from adults whereas IB suppressed the secretion of IL-1ra at higher concentrations only. At the same concentrations neither drug had an in vitro effect on the production of IL-1ra by CBMC of preterm newborns. In conclusion, the lower ability of CBMC of preterm newborns to produce IL-1ra in response to LPS and the absence of an IM and IB effect on the secretion of this cytokine by these cells as compared with PBMC of adults, suggest an underdevelopment of the immune response in preterm newborns.