Serum Levels Of IL-3 Research Articles

The association of IL-3, IL-17A, and IL 27 serum levels with susceptibility to toxoplasmosis in recurrent abortion of Iraqi women

Cytokines are a group of immunomodulatory proteins leading to a variety of immune reactions in the human; these cytokines play a significant role in the development of appropriate immune responses against T. gondii. This study aims to reveal the association of toxoplasmosis with serum levels of IL-3, IL-17A, and IL-27 in aborted women. The blood samples of patients and controls were collected from Al-Alawiya Maternity Teaching Hospital/Baghdad/Iraq from 2019 to 2020 for detecting anti-T. gondii antibodies (IgG and IgM) and the level of interleukins by ELISA. The results of TORCH by rapid test for recurrent abortion recorded 25.3% seropositive for anti-Toxoplasma antibodies, and 31.5% seropositive for one or more cases of TORCH test (Cytomegalovirus, Rubella, and Herpes). Whereas the results for anti-T. gondii IgG and IgM antibodies were shown elevated positivity percentages by ELISA test; these percentages were 56.2% in recurrent abortion women with significant differences (P < 0.05). The results suggested that the IL-3 serum concentration of pregnant women, recurrent abortion, and recurrent abortion with toxoplasmosis was declined versus healthy women with significant differences (p < 0.05). However, the results revealed that the concentration of IL-17A in recurrent abortion, and recurrent abortion with toxoplasmosis elevated versus healthy women and pregnant women with significant difference (p < 0.05). Whereas the results indicated that the IL-27 serum concentration elevated with significant differences in recurrent abortion with toxoplasmosis group compared to healthy women, pregnant women, and recurrent abortion. Interestingly, the serum levels for IL-27 increased comparing to the levels of IL-3 and IL-17A in all groups with significant differences (P < 0.05). In conclusion, it appeared in this study that the role of IL-3, IL-17A, and IL-27 in the maternal immune response during infections can lead to abortion.

SUN-051 Increased Circulating Cytokines in African American Women with Obesity and Elevated HbA1c

Background: The leading cause of death in US women is cardiovascular disease (CVD). Obesity and type-2 diabetes (T2D) are independent risk factors for cardiovascular disease while obesity is the leading risk factor for T2D. CDC reports that 53% of African American women are obese, compared to 32% of European American women. They also suggest that the prevalence of obesity may contribute to the increase in prevalence of diabetes; 85.2% of people with T2D are overweight or obese. The CDC estimates that 1 in 3 Americans will have diabetes by 2050, if this trend continues. Obesity, diabetes, and CVD are all associated with inflammation created by the expansion of adipose tissue. Low grade inflammation is associated with insulin resistance and precedes the onset of T2D in adults. Methods: A total of 30 serum samples were collected from African American women: 15 obese, normal HbA1c and 15 obese, high HbA1c. Clinical metabolic parameters were determined using standard commercial kits administered by Laboratory Corporation of America. Thirty chemokines/cytokines were measured using Luminex X-MAP® technology. Cytokine levels between the two groups were compared using unpaired t-test, followed by Pearson’s correlation coefficient (r) to determine correlation between cytokine expression and clinical metabolic parameters. Results: Serum levels of IL-3 (P=0.007), IL-4 (P=0.02), IL-7 (P=0.002), TNF-α (P=0.006), IFN-α2 (P=0.001) and CX3CL1 (P=0.02) were significantly higher in obese, African American women with elevated HbA1c. IL-7 (R=0.53, P=0.01) and TNF-α (R=0.37, P=0.04) were positively correlated with HbA1c in all patients. In patients with elevated HbA1c, IL-3 (R=-0.72, P=0.005) and IFN-α2 (R=-0.83, P=0.05) were negatively correlated with HbA1c. Several clinical metabolic parameters were also correlated with cytokines. TNF- α (R=0.48, P=0.008), IL-7 (R=0.58, P=0.005), CX3CL1 (R=0.50, P=0.006) and IFN- α2 (R=0.42, P=0.03) were positively correlated with triglycerides in all patients. TNF- α (R=0.49, P=0.007), IL-7 (R=0.58, P=0.005), CX3CL1 (R=0.50, P=0.006) and IFN- α2 (R=0.42, P=0.03) were positively correlated with VLDL in all patients. In patients with elevated HbA1c, IL-7 (R=-0.65, P=0.03) and IFN- α2 (R=-0.57, P=0.04) were negatively correlated with HDL. IL-7 (R=-0.58, P=0.005) was negatively correlated with HDL in all patients. Conclusions: Increased cytokine expression of IL-3, IL-4, IL-7, TNF- α, IFN- α2, and CX3CL1 is associated with T2D in obese, African American women. Circulating cytokine expression is associated with increased cardio-metabolic disease risk. Our observations provide insights into T2D and propose new avenues for therapeutic strategies to combat obesity and its associated metabolic abnormalities.

Role of interleukin-3 as a prognostic marker in septic patients.

ObjectiveTo evaluate the accuracy of IL-3 to predict the outcome of septic patients.MethodsProspective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality.ResultsOne hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio).ConclusionHigher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

Polysaccharides isolated from &lt;i&gt;Morinda officinalis&lt;/i&gt; How roots inhibits cyclophosphamide-induced leukopenia in mice

Purpose: To investigate the optimum parameters for extracting polysaccharides from Morinda officinalis How (MOP), and explore their inhibitory effects on leukopenia in mice. Methods: Orthogonal design was performed to investigate the optimum parameters for extracting MOP. A leukopenia mouse model was established by injection of cyclophosphamide (CTX) for three days. Thereafter, MOP (100, 200 and 400 mg/kg) was administered orally for 10 days. Furthermore, blood cells (leukocytes, neutrophil, lymphocyte and mononuclear cell) were analyzed, while serum IL-3 and IL- 6 were determined by ELISA. The thymus and spleen of the mice were separated and weighed to determine viscera indices. Results: Orthogonal design showed that the influence order of the four factors was extraction times (C) > ratio of water to raw material (RWM, D) > extraction time (B) > extraction temperature (A). The optimum extraction parameters for MOP were: extraction temperature (80 °C), extraction duration (2 h), no. of extractions (3), and ratio of water to raw material (30 mL/g). Furthermore, the results indicate that MOP (100, 200 and 400 mg/kg) elevated the levels of leukocyte ( p < 0.01), neutrophil ( p < 0.01), lymphocyte ( p < 0.01) and mononuclear cell ( p < 0.01) in leukopenia mice. Besides, MOP (100, 200 and 400 mg/kg) also increased thymus ( p < 0.01) and spleen ( p < 0.05) indices and serum levels of IL-3 ( p < 0.05) and IL-6 ( p < 0.01). Conclusion: Orthogonal design is a good strategy for optimizing extraction parameters of MOP. Furthermore, MOP stimulated synthesis of leukocytes in CTX-induced leukopenia in mice. Thus, MOP is a potential adjunct for the treatment of tumors/cancers. Keywords: Morinda officinalis , Polyscacharide, Orthogonal design, Leukopenia, Thymus index, Spleen index

Panax ginseng Modulates Cytokines in Bone Marrow Toxicity and Myelopoiesis: Ginsenoside Rg1 Partially Supports Myelopoiesis

In this study, we have demonstrated that Korean Panax ginseng (KG) significantly enhances myelopoiesis in vitro and reconstitutes bone marrow after 5-flurouracil-induced (5FU) myelosuppression in mice. KG promoted total white blood cell, lymphocyte, neutrophil and platelet counts and improved body weight, spleen weight, and thymus weight. The number of CFU-GM in bone marrow cells of mice and serum levels of IL-3 and GM-CSF were significantly improved after KG treatment. KG induced significant c-Kit, SCF and IL-1 mRNA expression in spleen. Moreover, treatment with KG led to marked improvements in 5FU-induced histopathological changes in bone marrow and spleen, and partial suppression of thymus damage. The levels of IL-3 and GM-CSF in cultured bone marrow cells after 24 h stimulation with KG were considerably increased. The mechanism underlying promotion of myelopoiesis by KG was assessed by monitoring gene expression at two time-points of 4 and 8 h. Treatment with Rg1 (0.5, 1 and 1.5 µmol) specifically enhanced c-Kit, IL-6 and TNF-α mRNA expression in cultured bone marrow cells. Our results collectively suggest that the anti-myelotoxicity activity and promotion of myelopoiesis by KG are mediated through cytokines. Moreover, the ginsenoside, Rg1, supports the role of KG in myelopoiesis to some extent.

Characteristic Proinflammatory Serum Cytokine Profiles In Patients with B-Cell Chronic Lymphocytic Leukemia

AbstractAbstract 3595 Background:Cytokines are posited to play a critical regulatory role on the survival of the B-cell neoplastic clone in Chronic Lymphocytic Leukemia (CLL). AIM: The primary goals of this study were 1) to define additional relevant cytokines, growth factors and chemokines in CLL pathophysiology and 2) to correlate abnormal cytokine levels with disease stage, relevant hematological data and multiple prognostic factors. METHODS: A novel bead-based protein array system was employed to simultaneously measure 38 proinflammatory cytokines in the sera of CLL patients (N=116) and healthy age and sex matched controls (N=30). These results were correlated with Rai stage, β2-microglobulin level, LDH, CD38 expression and cytogenetic abnormalities. RESULTS: We first confirmed previous observations that TNFα, IL-1α, IL-1RA, IL-10, sIL-2Rα, VEGF and sCD40 ligand are significantly elevated in patients with CLL as compared with healthy controls. Expanding on the current literature, we demonstrated perturbations in an additional 15 serum cytokines in affected individuals. Compared to healthy controls, CLL patients had an increase in serum levels of IL-3 (p=0.002), IL-7 (p=0.008), INF-2α (p<0.0001), MCP-1 (p<0.0001), MIP-1β (p=0.002), MDC (p<0.0001), Fractakine (p<0.0001), EGF (p<0.0001), FGF-2 (p<0.0001), GRO (p<0.0001), Eotaxin (p<0.0001) and FLT-3 ligand (p<0.0001). Patients with CLL also exhibited significantly lower levels of INF-γ (p<0.01), IL-6 (p<0.005) and IL-8 (p<0.002) when compared to healthy individuals. Advanced Rai stage and high risk chromosomal abnormalities (del 11q and del 17p) strongly correlated with higher serum levels of TNFα, soluble IL-2Rα, IL-10, MCP-1, MIP-1α, MIP-1β and IP-10. Finally, serum levels of TNFα, MIP-1α and MIP-1β correlated with other adverse prognostic markers, including total white blood cell count, serum β2-microglobulin and LDH levels as well as CD38 expression. CONCLUSION: We have demonstrated numerous previously unrecognized cytokine abnormalities in patients with CLL and described a unique cytokine signature associated with advanced disease. Supported by the current understanding of cytokine biology and CLL pathophysiology, our observations suggest an important regulatory role for hematopoietic cytokines, such as IL-3 and IL-7, in promulgating survival of the aberrant B-cell clone. Likewise, the profoundly high levels of chemokines (i.e. MCP-1, MIP-1α, MIP-1β, IP-10) and their association with high risk prognostic factors argue for their role in sustaining the neoplastic microenvironment. Finally, the altered levels of IL-10, IL-6 and INF-γ observed in patients with CLL likely contribute to the immunosuppressive phenotype of the disease state. Disclosures:No relevant conflicts of interest to declare.

Results of a phase I study in patients suffering from secondary-progressive multiple sclerosis demonstrating the safety of the amino acid copolymer PI-2301 and a possible induction of an anti-inflammatory cytokine response

PI-2301 is an immunomodulator that could be an alternative therapy for MS. A placebo-controlled, multiple-ascending dose, double-blind study was performed in patients with secondary-progressive MS. Treatment was given subcutaneously once weekly for 8 weeks, followed by a 4-week open-label treatment period with active drug. The most common adverse event was transient injection site reactions. Non-significant trend for increases in serum levels of IL-3, IL-13, and CCL22 over time were suggestive of a beneficial T H2 immune response in subjects dosed with PI-2301 at 3 and 10 mg. MRI data indicated a non-significant trend for a reduction of lesion numbers in subjects treated with 1 and 3 mg PI-2301.

IN VIVO DIFFERENTIATION OF TOLEROGENIC DENDRITIC CELLS IN THE LIVER, AN INSIGHT INTO HEPATIC TOLERANCE

P908 Aims: Discovery of liver transplant tolerance has led to an enthusiasm of investigating liver dendritic cells (DC) which play a key role in determining immunity and tolerance. Recent in vivo demonstration of myeloid CD11c+ hepatic DC with strong capacity to stimulate T cells certainly supports the notion that hepatic DC generate immunity. There is however, lacking of evidence of existence of liver tolerogenic DC in vivo. Methods and Results: We adopted, in this study, an aaproach to transfect gene(s) in the liver by tail vein rapid injection of naked plasmid carrying genes encoding IL-3, CD40L or GM-CSF, (GFP as reporter) into B6 (H-2b) mice, which enabled significant levels of transgene expression in the liver in 8h, reached the peak in 24 hr, decreased thereafter, and lasted for 5-7 days, as demonstrated either by detection of GFP with fluorescent microscopy or by serum levels of IL-3 with ELISA. While we confirmed the expansion of mixed population in the group of transfection with GM-CSF, most of them morphologically resembled myeloid DC, and located in portal and periportal areas. Another more homogeneous population was identified following transfection with IL-3 plus CD40L, not IL-3 alone, which is morphologically distinctive from myeloid DC and form big aggregates in expanded lobules as well as portal and periportal areas. FACS analysis revealed that in addition to common DC surface markers (MHC class II, CD80, CD86, and CD40), they were B220+, CD205+, but CD11b- and CD11c-, and expressed high TLR-9, but low TLR-4. We examined their response to bacterial stimuli. Not surprising, after LPS stimulation, the co-stimulatory molecule expression was upregulated, similar to myeloid DC, but what differ are their cytokine profiles. Demonstrated by RNAse protection assay, B220+/CD205+ DC expressed defective IL-12 mRNA with only p35 but not p40 mRNA, and up-regulated IL-10 but down-regulated IL-1 expression. In contrast, myeloid hepatic DC showed cross-board upregulation of inflammatory cytokine, including IL-1α, β, IL-6 and IL-12 (both p35 and p40). We studied in vitro DC-T cell interaction in an antigen-specific manner. Using both CD4 (DO10.11) and CD8 (Des) TCR transgenic T cells. In comparison to myeloid DC, B220+/CD205+ DC induced hyporesponsiveness of both CD4 and CD8 T cells measured by thymidine uptake with repressed levels of IL-2 (1.0 ng/ml vs 2.6 ng/ml), but similar level of IFN-γ (8.3 ng/ml vs 8.2 ng/ml). This hyporesponsiveness is not due to failure of T cell activation since CFSE-labeling showed T cell dividing similar to culture with myeloid DC. It appeared to result from shortened T cell survival. In contrst to myeloid DC administration of which exacerbated B6 cardiac allograft rejection in C3H (H-2k) recipients, B220+/CD205+ DC prolonged allograft survival. Conclusion: A tolerogenic DC population in the liver was differentiated in vivo, which may play an important role in balancing hepatic T cell immunity and tolerance.

Theophylline induces apoptosis of the IL-3 activated eosinophils of patients with bronchial asthma.

In bronchial asthma, eosinophils are upregulated and their survival is suggested to be prolonged by the action of some cytokines such as Interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). We find here that the survival of eosinophils in the peripheral blood of patients with asthma is correlated with the serum levels of IL-3 but not of IL-5 and GM-CSF. Interestingly, theophylline is revealed to induce apoptosis of the prolonged survival eosinophils by IL-3, as judged by morphological changes and nucleosomal DNA fragmentation. During the apoptosis, caspase-3 in eosinophils stimulated by IL-3 is activated by theophylline. The substrate of caspase-3, poly (ADP-ribose) polymerase (PARP), is cleaved in the eosinophils after theophylline treatment. These results suggest that theophylline is able to induce apoptosis of the IL-3 activated eosinophils in patients with bronchial asthma, and that its clinical effectiveness may be due to the reduction of inflammatory cells in the airway.