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Background: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth., Methods: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software., Results: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01)., Conclusions: The inflammatory biomarkers IL-1β, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.

The aim of this study was to evaluate cytokine levels (IL-2, IL-8, TNF-α, IL-5, IL-6 and IL-10) in the peritoneal fluid in non-neoplastic tumours, benign ovarian neoplasms and malignant ovarian neoplasms. Peritoneal fluid or ascites was collected from 117 patients with neoplastic and non-neoplastic ovarian tumours. Cytokine levels were assessed by ELISA. The unpaired groups were compared by the Kruskal-Wallis test with Dunn's post-test. Higher IL-6 levels were found in malignant neoplasms when compared to non-neoplastic tumours ( p =.0241). There was no significant difference in the evaluation of other cytokines. Therefore, higher IL-6 levels in peritoneal fluid are related to the diagnosis of ovarian cancer. Further studies should be performed to evaluate the profile of cytokines in the peritoneal fluid of patients with ovarian tumours, and may be a new diagnostic strategy and a future target for treatment.Impact statement What is already known on this subject? Cytokines can be dosed in both the serum and peritoneal fluid, and in the ascitic fluid of women with ovarian neoplasia. Elevated levels of IL-6 were found in the ascitic fluid of patients with malignant ovarian tumours. What the results of this study add? To our knowledge, this is the first study in the literature that evaluates a large panel of cytokines in the peritoneal fluid (and not only in ascites), comparing non-neoplastic tumours, benign neoplasms and malignant ovarian neoplasms. What the implications are of these findings for clinical practice and/or further research? The cytokine dosage in the peritoneal fluid should be considered to map a profile of inflammatory cytokines that permeate the peritoneal cavity of patients with ovarian cancer. The dosage of these cytokines can be a potential pre-surgical tumour marker. In addition, a better understanding of the pattern of cytokines around ovarian neoplasia may be targeted for further studies in the development of new therapies for ovarian cancer.

The purpose of this study was to investigate the stress-reactivity of the anti-inflammatory cytokine, IL-10, in saliva and to determine how salivary IL-10 levels change in relation to those of IL-1β, a pro-inflammatory cytokine, following stress. Healthy young adults were randomly assigned to retrieve a negative emotional memory (n = 46) or complete a modified version of the Trier Social Stress Test (n = 45). Saliva samples were taken 10 min before (baseline) and 50 min after (post-stressor) onset of a 10-min stressor, and were assayed using a high sensitivity multiplex assay for cytokines. Measurable IL-10 levels (above the minimum detectable concentration) were found in 96% of the baseline samples, and 98% of the post-stressor samples. Flow rate-adjusted salivary IL-10 levels as well as IL-1β/IL-10 ratios showed moderate but statistically significant increases in response to stress. Measurement of salivary IL-10 and pro-/anti-inflammatory cytokine ratios may be useful, noninvasive tools, in stress research.

Objective: To compare interleukine-10 (IL-10) and total antioxidant capacity (TAC) levels after breast milk storage by studying premature and term mothers’ colostrum and mature milk and by analyzing those levels relative to gestational week., Methods: Fifty-four colostrum and mature breast milk samples were collected from both premature and term mothers. The samples were divided into three groups based on the time of analysis: fresh milk, at +4 °C for 72 h, and at -20 °C for 14 d. The IL-10 and TAC levels were measured quantitatively., Results: Fresh colostrum and mature milk had similar IL-10 levels. Term mothers’ fresh-colostrum TAC levels were higher than their mature milk. The mature milk of the premature mothers’ had higher TAC levels than that of term mothers. Storage did not affect the IL-10 levels of breast milk, but fresh milk antioxidant capacity halved after 72 h and 14 d. Colostrum IL-10 and TAC levels did not correlate with gestational week. Mature milk IL-10 levels did not correlate with gestational week, but TAC levels negatively correlated with gestational week (r: -0.61: p < 0.01)., Conclusions: The milk stored for 72 h at +4 °C and for 14 d at -20 °C did not maintain the same TAC levels as the fresh samples. This should be considered especially for sick infants who need more antioxidant capability in neonatal units.

Background: In a previous study, we demonstrated that the human macrophage migration inhibitory factor (MIF)-like protein (As-MIF) isolated from helminths could inhibit allergic airway inflammation via the recruitment of CD4(+)CD25(+)Foxp3(+) T cells., Objective: To evaluate the clinical importance of As-MIF as an antiasthma drug, we evaluated immune responses after recombinant As-MIF (rAs-MIF) treatment in peripheral blood mononuclear cell (PBMC) cultures., Methods: PBMC was isolated from 10 patients with atopic asthma, 8 patients with nonatopic asthma, and 12 nonatopic healthy subjects, and various concentrations of rAs-MIF were transferred into the PBMC culture medium. After 3 days, we measured the levels of T helper 2 and T helper 1 cytokines via ELISA., Results: In atopic asthma, IL-4 and IL-5 production was significantly reduced in the PBMC cultures after rAs-MIF treatment. These inhibitory effects were not observed in the nonatopic asthma group. By way of contrast, IL-10 production in the PMBC cultures was significantly increased after rAs-MIF treatment in all experimental groups., Conclusion: The results of this study are similar to those previously reported in a mouse study, suggesting that As-MIF might be a candidate for the specific treatment of asthma.

The objective of this study was to evaluate the immunomodulatory effects of cinobufagin (CBG) isolated from Chan Su (Venenum Bufonis) in vitro. In this paper, our results show that CBG significantly stimulated cell proliferation of splenocytes and peritoneal macrophages (PMΦ) and markedly enhanced the phagocytic activation of PMΦ. CBG also significantly increased CD4(+)CD8(+) double-positive T-cell populations and the percentage of S-phase cells of splenic lymphocytes. The levels of several Th1 cytokines, including interferon-γ and tumor necrosis factor-α, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased. As a result, the ratio of Th1/Th2 also increased. Taken together, these results indicated that CBG had potential immune system regulatory effects and suggested that this compound could be developed as a novel immunotherapeutic agent to treat immune-mediated diseases such as cancer.

The tendency of immune response toward either Th1 or Th2 cytokine pattern can cause a number of pathologic conditions. Multiple sclerosis is postulated to be a Th1-type cell-mediated autoimmune disease. MS14--an Iranian natural product--seems to possess anti-inflammatory properties. Thus, we studied the effect of orally administered MS14 on Th2 cytokines (IL-5 and IL-10) in normal Balb/C mice (100 mg/kg; 5 days). The result indicated that activated splenocytes of MS14 group produced significantly more IL-5 and IL-10 (3-4 times in comparison with control group mice). MS14 could upregulate Th2 cytokine and thereby it may possess immunoregulatory properties probably useful in treatment of some diseases.

Objective: The anti-inflammatory limb of the immune response is crucial for dampening inflammation. Spontaneous parturition at term and preterm labor (PTL) are mediated by inflammation in the cervix, membranes, and myometrium. This study focuses on the changes in the amniotic fluid concentrations of the anti-inflammatory cytokine interleukin (IL)- 10. The objectives of this study were to determine whether there is a relationship between amniotic fluid concentrations of IL-10 and gestational age, parturition (at term and preterm), and intra-amniotic infection/inflammation (IAI)., Study Design: A cross-sectional study was conducted including 301 pregnant women in the following groups: (1) mid-trimester of pregnancy who delivered at term (n = 112); (2) mid-trimester who delivered preterm neonates (n = 30); (3) term not in labor without IAI (n = 40); (4) term in labor without IAI (n = 24); (5) term in labor with IAI (n = 20); (6) PTL without IAI who delivered at term (n = 31); (7) PTL without IAI who delivered preterm (n = 30); (8) PTL with IAI who delivered preterm (n = 14). IL-10 concentrations in amniotic fluid were determined by a specific and sensitive immunoassay. Non-parametric statistics were used for analysis., Results: (1) IL-10 was detectable in amniotic fluid and its median concentration did not change with gestational age from mid-trimester to term. (2) Patients in labor at term had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term not in labor (p = 0.04). (3) Women at term in labor with IAI had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term in labor without IAI (p = 0.02). (4) Women with PTL and IAI who delivered preterm had a significantly higher median amniotic fluid concentration of IL-10 than those without IAI who delivered preterm and than those who delivered at term (p = 0.009 and p < 0.001, respectively). (5) Among patients with preterm labor without IAI, those who delivered preterm had a significantly higher median amniotic fluid IL-10 concentration than those who delivered at term (p = 0.03)., Conclusions: The anti-inflammatory cytokine IL-10 is detectable in the amniotic fluid of normal pregnant women. Spontaneous parturition at term and in preterm gestation is associated with increased amniotic fluid concentrations of IL-10. IAI (preterm and at term) is also associated with increased amniotic fluid concentrations of IL-10. We propose that IL-10 has a role in the regulation of the immune response in vivo by initiating actions that dampen inflammation.

Objective: Signal transducers and activators of transcription (STATs) are crucial mediators of cytokine signalling. Constitutive activation of STATs, especially STAT3, has been reported in several diseases. Primary Sjögren's syndrome (pSS) is associated with overproduction of cytokines such as interleukin-10 (IL-10), although the mechanism by which this occurs is unknown. As STAT3 is a potent inducer of IL-10, this study focused on determining the pattern of STAT3 activation in peripheral lymphocytes from patients with pSS., Methods: Twelve pSS patients and 12 healthy age-matched control subjects were studied. Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation. Phosphorylated STAT3 (pSTAT3) and also STAT3 expression were determined by flow cytometry in gated CD3(+ )and CD19(+) lymphocytes. Similarly, pJak1 and pTyk2 were also determined in gated CD3(+) lymphocytes., Results: Although the protein expression of STAT3 was similar among controls and pSS patients, we found that STAT3 was constitutively activated in CD3(+) lymphocytes from pSS patients. Neither Jak1 nor Tyk2 (the upstream activators of STAT3) was activated in pSS CD3(+) lymphocytes, suggesting that the constitutive activation of STAT3 observed in pSS patients might not depend on cytokine stimulation but instead might be the result of an abnormal inactivation of pSTAT3., Conclusions: These data provide evidence of abnormal STAT3 signalling in T cells from pSS patients.

Detection of cytokines secreted by ex vivo antigen-stimulated peripheral blood mononuclear cells (PBMC) by ELISA is hampered by low frequencies of specific T cells and cellular receptor consumption. We investigated if ELISpot, measuring cytokine production at the single cell level, facilitated a better detection of the Th2 cytokines IL-4 and IL-5. PBMC from nickel-allergic (n = 31) and non-allergic subjects (n = 10) were stimulated with nickel or tetanus toxoid (TT) and cytokine production assessed by ELISpot and ELISA. By IL-4 ELISpot, 74% of the allergic and 0% control subjects responded to nickel and 56% of all subjects to TT. ELISA detected IL-4 after nickel stimulation only in 13% of the allergic subjects. Also detection of TT-induced IL-5 was improved by ELISpot with 54% subjects responding versus 24% in ELISA. In contrast, detection of nickel-induced IL-5 was more comparable between methods, most likely due to the 7-fold higher IL-5 production per cell in response to nickel versus TT. The low IL-5 response to TT was associated with a higher induction of the down-regulatory cytokine IL-10 by TT as compared to nickel (p < 0.001). Overall, ELISpot displayed a better detection of IL-4 as well as low intensity IL-5 responses thus emphasizing the importance of selecting suitable methods for the measurement of cytokine production ex vivo.

Background: There is complicated pathogeny involved in spontaneous abortion. At present, the focus of study is on the interface between mother and fetus, the trophoblasts. Indoleamine 2,3-dioxygenase (IDO) is the first and regulatory enzyme in the major route of l-tryptophan catabolism, which induces immunosuppression of T lymphocytes. In the present study we investigated the effect of Kidney-replenishing herb on the expression and activity of IDO in human syncytiotrophoblasts cultured in vitro and the balance of helper T cell (Th) cytokines., Methods: Syncytiotrophoblasts were cultured in vitro for 24, 48 or 72 h, with either control serum or serum made from Kidney-replenishing herb, without or with different concentrations of the IDO inhibitor 1-methyltryptophan (1-MT). Reverse transcription-polymerase chain reaction was applied to analyze the IDO mRNA transcription of syncytiotrophoblasts and Western blotting was applied to determine the expression of IDO protein in syncytiotrophoblasts. The concentration of interleukin-10 and interferon-gamma in co-culture medium of syncytiotrophoblasts and decidual T lymphocytes was determined by enzyme-linked immunosorbent assay. High-performance liquid chromatography was used to determine the concentration of kynurenine (Kyn) and tryptophan (Tyr) in the co-culture medium, and the ratio of Kyn/Try was used to assess IDO activity., Results: IDO mRNA and protein were detected in human syncytiotrophoblasts cultured in vitro. The IDO inhibitor 1-MT caused the balance of Th cytokines to depart from type 2; when IDO activity was inhibited, Kidney-replenishing herb improved the expression of IDO mRNA and protein, promoted IDO activity and caused the balance of Th cytokines depart from type 1., Conclusion: Kidney-replenishing herb improves the expression of IDO mRNA and protein, promotes IDO activity to an appropriate value, resumes the balance of Th cytokines and regulates maternofetal tolerance.

We investigated the immunomodulatory activity of allogenic whole tumor cell vaccine in oral cancer patients in vitro by two-color flow cytometry. Vaccine treatment significantly increased the expression of CD69 and HLA-DR in CD3+ T-cell subsets. The frequency of Interferon-gamma and Interleukin (IL)-2 expressing CD4+/CD8+ T-cell subsets was significantly higher with a concomitant reduction in IL-4 and IL-10 expressing T-cells in the vaccine treated group as compared with the untreated controls. Vaccine treatment significantly increased T-cell receptor (TCR), Vbeta3, Vbeta5 and Vbeta8 usage. The results indicate that the allogenic whole tumor cell vaccine is able to trigger T-cell mediated immunity in patients with intraoral squamous cell carcinoma.

Some types of antimicrobial agents such as fosfomycin, clarithromycin, and erythromycin have been known to affect the host's immunological response. We investigated whether itraconazole (ITCZ) can modulate the serum cytokine levels (tumor necrosis factor (TNF-alpha, interleukin (IL)-10, IL-12p40) in both patients and healthy subjects. Serum samples were collected and TNF-alpha, IL-10 and IL-12p40 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). We showed increased levels of IL-12p40 in patients treated with ITCZ. In healthy subjects, moreover, ITCZ treatment significantly increased the production of IL-12p40, but not TNF-alpha or IL-10. These findings suggest that the effectiveness of ITCZ in the treatment of fungal infection may be due not only to its direct antifungal effect, but also to induction of an immunomodulative effect on the host defense systems by regulation of cytokine production.

Diagnosis of an exposure to airborne toxicants can be problematic. Phosgene is used widely in industry for the production of many synthetic products, such as polyfoam rubber, plastics, and dyes. Although nearly 100% of the gas is consumed during processing, there is the potential problem of accidental or even intentional exposure to this irritant/choking agent. Exposure to phosgene has been known to cause latent life-threatening pulmonary edema. A major problem is that there is a clinical latency phase from 3 to 24 h in people before irreversible acute lung injury occurs. Assessment of markers of acute lung injury after a suspected exposure would be useful in developing rational treatment strategies. These experiments were designed to assess bronchoalveolar lavage fluid (BALF) for the presence of the early markers of exposure to phosgene in mice from 1 to 72 h after exposure. Separate groups of 40 CD-1 male mice (Crl:CD-1(ICR)BR) weighing 29 +/- 1 g were exposed whole-body to either air or a concentration x time (c x t) amount of 32 mg/m(3) (8 ppm) phosgene for 20 min (640 mg x min/m(3)). BALF from air- or phosgene-exposed mice was taken at 1, 4, 8, 12, 24, 48, and 72 h postexposure. After euthanasia, the trachea was excised, and 800 micro l saline was instilled into the lungs and washed 5x. BALF was assessed for interleukin (IL)-4, IL-6, tumor necrosis factor (TNF) alpha, IL-1alpha, macrophage inflammatory protein (MIP)-2, and IL-10. At 4 h postexposure, IL-6 was 15-fold higher for phosgene-exposed mice than for the time-matched air-exposed control group. At 8 and 12 h, IL-6, IL-1beta, MIP-2, and IL-10 were significantly higher in phosgene-exposed mice than in time-matched air-exposed controls, p < or = 0.05 to p < or = 0.001, whereas TNF alpha reached peak significance from 24 to 72 h. IL-4 was significantly lower in the phosgene-exposed mice than in the air-exposed mice from 4 to 8 h after exposure. These data show that BALF is an important tool in assessing pro- and anti-inflammatory markers of phosgene-induced acute lung injury and that knowledge of these temporal changes may allow for timely treatment strategies to be applied.

The release of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 upon stimulation with non-viable conidia and hyphal fragments from Aspergillus fumigatus was investigated in an ex vivo whole-blood model. In healthy volunteers, high numbers of conidia (between 10(6) and 3 x 10(8)/ml) induced a moderate release of TNF-alpha and IL-6. Hyphal fragments (2.5 x 10(5)/ml) were more potent in stimulating the release of these pro-inflammatory cytokines. Although some IL-10 release was observed upon stimulation with either conidia or hyphal fragments, it was not significantly different from that in unstimulated controls. In comparison, in whole blood obtained from 4 patients with chronic granulomatous disease (CGD), a high release of pro-inflammatory cytokines together with a significantly higher IL-10 release than in the healthy controls was seen after stimulation with A. fumigatus. In conclusion, A. fumigatus can trigger the release of pro-inflammatory cytokines in a human whole-blood system, which is likely to be central to the activation of antifungal defence mechanisms. In contrast, A. fumigatus stimulates a higher release of anti-inflammatory cytokines in CGD patients, which may suggest that a dysregulation between pro- and anti-inflammatory cytokines contributes to the increased susceptibility to invasive aspergillosis in this patient group.

Objective: To analyse proinflammatory Th1 and Th2 cytokines in patients with Behçet's disease (BD) in relation to disease activity., Methods: Forty-five BD patients (25 in active stage) were investigated with ELISA for estimation of cytokines levels. Furthermore, cytokines intracellular synthesis (IL-4 and IFN-gamma) of CD4+ T cells was studied., Results: Active and in remission BD patients showed increased serum levels of Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-6 and IL-10) cytokines. Active BD was characterized by a higher increase of IL-6, IL-10 and a striking increase of IL-17, IL-18 and IFN-gamma, compared to remission RD. Upon in vitro stimulation, the percentages of CD4+ T cells containing IFN-gamma and CD40L were higher in active BD compared to healthy controls., Conclusion: Our results suggest that the microenvironment of CD4+ T cells in active BD may induce the production of more cells committed to Th1 than in BD patients in remission and healthy controls.

Background: Transgenic rats expressing HLA-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis resembling human inflammatory bowel disease. We investigated the sequential changes in the luminal bacterial flora and mucosal cytokine mRNA expression in this model., Methods: HLA-B27 rats were maintained in a specific pathogen-free environment, and luminal microflora was evaluated by standard bacterial culture technique. The expression of mucosal cytokine mRNA was analysed by RT-PCR methods., Results: Clinical symptoms of colitis appeared at 8 weeks of age. The total number of obligate anaerobes was higher than those of facultative anaerobes during the experimental period. At 6 weeks of age, the colonization of Bacteroides spp., Bifidobacterium spp. and Lactobacillus spp. was already detectable at high concentrations, whereas Clostridium spp. and Eubacterium spp. were not detected. The expression of proinflammatory cytokines (IL-Ibeta, IL-8 and TNF-alpha) appeared at 8 weeks of age, and these were detectable until 17 weeks. A similar pattern was observed in the expression of Th1 cytokines (IL-2, IL-12 and IFN-gamma). On the other hand, the expression of Th2 cytokines (IL-4, IL-10 and TGF-beta) was weak. IL-4 mRNA expression was weakly detectable only at 6 and 8 weeks of age. The expression of IL-10 and TGF-beta mRNA was scarcely detectable throughout the experimental period., Conclusion: The development of colitis may be mediated by both the predominant expression of Th1 cytokines and the weakness of Th2 cytokine expression in the mucosa. The colonization of anaerobic bacteria, especially Bacteroides spp., may be initiating and promoting these cytokine responses.

The pathophysiology of hypergastrinemia in H. pylori infection has been largely investigated and different reports clearly show that the infected antrum has a marked inflammatory response with a suggestive local production of cytokines. Notwithstanding, a few data are available on the circulating levels of cytokines and gastrin in the asymptomatic people carrying H. pylori infection. Thus, aim of the study was to evaluate circulating proinflammatory cytokines [Interleukin (IL)-8, Interleukin (IL)-10, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF)-alpha] and gastrin levels in H. pylori positive asymptomatic subjects vs. H. pylori negative ones. To this end, thirty healthy volunteers with no digestive symptoms or systemic disease were enrolled and H. pylori infection was identified by a 13C-urea breath test. Plasma levels of gastrin were determined using the RIA kit whereas IL-8, TNF-alpha, IL-10, and IFN-gamma levels in serum were measured with a solid-phase ELISA. Fifteen infected people showed significantly higher gastrin and TNF-alpha levels than uninfected subjects. On the contrary, IL-8 levels were significantly higher in the uninfected subjects than in H. pylori positive ones (P < 0.0422). IFN-gamma and IL-10 circulating levels were not affected by H. pylori presence, being not significantly different in the two groups.

Objective: In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation., Methods: The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry., Results: Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha production may not be due to down-regulation of cyclooxygenase activities., Conclusion: The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug.

A successful pregnancy has been postulated to be the result of a discrete balance between T-helper 1 (Th1) and T-helper 2 (Th2) type cytokines involved in growth and development of the conceptus. The aim of the present study was to examine the effect of Th1 cytokines (interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha)) on the release of Th2 cytokines including IL-6 and IL-10 by trophoblast cells obtained from term placenta. Trophoblast cells isolated by enzymatic disaggregation and Percoll gradient fractionation were cultured in supplemented medium alone or with varying concentrations of the selected recombinant cytokines. After 48 h of incubation, samples of the culture supernatant were analyzed for the Th2 cytokines IL-6 and IL-10 using specific ELISA assays. Both IL-1 beta and TNF alpha had no effect on the cell number and viability as determined by MTT assay. IL-1 beta significantly stimulated trophoblast release of IL-6 in a dose-dependent manner (3.3-, 5.5-, 10.3- and 22.4-fold higher compared to the control at 10, 50, 100, 500 U IL-1 beta/ml respectively, p < 0.05). TNF alpha also stimulated release of IL-6 by these cells. However, the stimulation at lower concentrations was not very high and a significant (p < 0.05) stimulation was observed only at higher concentrations (1.1-, 1.3-, 2.6- and 5.9-fold higher at 500, 1000, 1500, 2000 U TNF alpha/ml respectively). In contrast, neither IL-1 beta or TNF alpha exerted any significant effect on IL-10 release by term trophoblast cells (p > 0.05). The results of this study provide evidence that production of Th2 cytokines might be under the control of different regulatory pathways.

Levels of tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-10 and transforming growth factor (TGF)-beta in cerebrospinal fluid (CSF) and serum of 29 patients with multiple sclerosis (MS) of the relapsing-remitting type and of 20 controls with other non inflammatory neurological diseases were studied. Sixteen patients were in the active phase of disease and 13 in remission. In CSF, higher IL-10 and TGF-beta concentrations were found in patients with a stable phase of MS, while in the active phase there were elevated levels of TNF-alpha and GM-CSF. These results suggest that a different cytokine pattern could be probably involved in the pathogenesis of relapsing-remitting MS.