Interleukin‐15 blocks apoptosis and induces proliferation of the human myeloma cell line OH‐2 and freshly isolated myeloma cells
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The growth factor‐dependent myeloma cell line OH‐2, which has previously been shown to be responsive to interleukin (IL)‐6, tumour necrosis factor (TNF)‐α and lymphotoxin, was examined for response to other growth factors. Enhanced proliferation was found in the presence of IL‐10, IL‐15, IL‐2 and insulin growth factor (IGF)‐1. Proliferation was strongest in response to IL‐6, intermediate and roughly equipotent in response to IL‐15, IL‐10 and TNF‐α, and modest in response to IL‐2 and IGF‐1. IL‐15 was synergistic with TNF‐α, whereas combinations of IL‐15 and the other cytokines were merely additive. IL‐15‐induced proliferation could not be blocked by neutralizing antibody against gp 130, the common transducer chain of IL‐6 and related cytokines. IL‐15 and IL‐6 prevented apoptosis equally well, both better than TNF‐α, IL‐10, and IGF‐1. In four out of six samples of purified primary cells, IL‐15 and IL‐6 induced proliferation. Furthermore, IL‐15 mRNA was detected by RT‐PCR in most myeloma cell lines and freshly isolated purified patient samples. IL‐15 protein was detectable only in one out of about 20 tested cell supernatants from patients and myeloma cell lines. The OH‐2 cell line is multi‐responsive to cytokines and is a good system for the study of integration of cytokine signal transduction and growth control in myeloma. IL‐15 represents a novel modality of growth regulation in myeloma.Cytokines play a crucial role in the host's immune response. In melanoma patients, cytokine profiles seems to be related to the clinical course and their imbalance could be associated to tumour progression. Thus, we studied a panel of baseline cytokines and their behaviour during treatment in order to verify their correlation with clinical outcomes. Interleukin-6, interleukin-8, interleukin-10, interleukin-12 and soluble receptor of interleukin-2 were evaluated in 90 out of 176 metastatic melanoma patients enrolled in a phase III study comparing chemotherapy and biochemotherapy. We divided patients into three different groups according to their own cytokine levels (low, intermediate and high) and then we correlated these groups with some clinical features. We also monitored the cytokines during the treatment in a subgroup of 37 patients. In univariate analysis, higher values of interleukin-6 (P = 0.005), soluble receptor of interleukin-2 (P = 0.001) and interleukin-12 (P = 0.010) were correlated with a worse survival. Conversely, interleukin-8 was unable to discriminate patients with different prognoses, and interleukin-10 was undetectable in the majority of patients. In multivariate analysis, only soluble receptor of interleukin-2 maintained its independent role in survival. The impact of baseline cytokines on response was insignificant. Regarding the behaviours of cytokines during treatment, the most remarkable aspect was a progressive increase of interleukin-12 and soluble receptor of interleukin-2 in patients with a better survival. In our metastatic melanoma patients, higher basal levels of interleukin-6, interleukin-12 and soluble receptor of interleukin-2 were associated with a worse survival. In contrast, a progressive increase of interleukin-12 and soluble receptor of interleukin-2 was observed during treatment in patients with a better survival.
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Methylcholanthrene
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Interleukin 1β
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Objective To examine the expression of the cytokines of Th1(Interleukin 2) and Th2 (Interleukin 10) on the peripheral blood mononuclear cell (PBMC) of normal pregnant women and recurrent spontaneous abortion (RSA) patients. Methods The Interleukin 2 and Interleukin 10 mRNA were determined from PBMCs of 10 normal non pregnant women, 10 normal pregnant women and 10 patients with RSA by semi quantitative reverse transcriptional polymerase chain reaction (RT PCR) method. Results Comparing with the non pregnant women the Interleukin 10 mRNA was higher in normal pregnant women; the Interleukin 10 mRNA was lower, and the Interleukin 2 mRNA was higher in RSA women. And the Interleukin 10 mRNA was lower, while the Interleukin 2 mRNA was higher in RSA women compared with the normal pregnant women. Conclusion The results suggest that in normal pregnancy main secretion is Interleukin 10. It may cause RSA, when Interleukin 10 mRNA decreases while Interleukin 2 mRNA increases in pregnant women.
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Interleukin (IL)-1beta may effectively decrease introcular pressure (IOP) when administered by subconjunctival injection in normal rabbit. However, IL-1beta is a large molecular agent and an inflammation factor. The aim of this study was to evaluate the penetrability of IL-1beta, and the concentrations of both tumor necrosis factor (TNF)-alpha and IL-6 in the aqueous humor of normal rabbits treated with IL-1beta.A total of 170 rabbits were used in the study and were assigned to several different treatment groups as follows: 125 of the rabbits were assigned to two groups. In one group, 33 rabbits were injected subconjunctivally with IL-1beta and 39 were injected with saline alone. In the other group, 27 rabbits were given eye drops containing IL-1beta (400 ng/ml) and 26 were given saline alone. Aqueous humor (AH) was drawn and the concentration of IL-1beta within the fluid measured. The IOP was measured in another six rabbits after administration of eye drops containing IL-1beta (400 ng/ml). A further 20 rabbits were assigned to 3 groups as follows: eight untreated normal controls; six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of TNF-alpha in the fluid was measured. Another 19 rabbits were assigned to 3 groups as follows: seven untreated normal controls; and six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of IL-6 in the fluid measured. Measurement of cytokine concentration was by radio-immunoassay in all cases.The IL-1beta concentration in the AH was higher in those animals in which it had been administered subconjunctivally (P < 0.01). The IL-1beta concentration in the AH of the animals given eye drops was almost the same as that in the controls (P > 0.05). The administration of IL-1beta in the form of eye drops had little effect upon IOP reduction. Lower TNF-alpha concentrations were seen in the AH after the subconjunctival administration of IL-1beta, but the concentration of IL-6 was the same as in the normal controls.IL-1beta shows good corneal penetrability after subconjunctival injection into normal rabbit eyes. The IOP reduction induced by IL-1beta is unlikely be associated with an inflammatory response.
Lagomorpha
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Aim: Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA).
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Intrauterine growth restriction
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Polymyalgia rheumatica and giant cell arteritis are diseases which are characterized by a brisk acute phase response. Cytokines, principally interleukin-1 and interleukin-6, are thought to mediate the release of acute phase proteins from hepato cytes. Employing a sensitive bioassay based on the hybridoma growth factor properties of interleukin-6, we investigated its levels in sequential sera obtained from 15 initially untreated patients with PMR/GCA. We found that interleukin-6 activity was significantly elevated in all untreated patients. Although there was a significant decline in its levels after suc cessful steroid therapy, seven patients continued to have raised serum levels of interleukin-6 for up to 6 months after initia tion of treatment. Activated endothelial cells are a potent source of interleukin-6 and its persistence in the circulation may be taken as evidence of continuing disease activity. What is not explicable is the normalization of the acute phase response soon after the commencement of steroid therapy when circulating levels of interleukin-6 are still high. This suggests that steroids may be having additional effects on hepatocyte function.
Polymyalgia rheumatica
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Objective:To analysis the role and clinical significance of interleukin-10(IL-10),interleukin-17(IL-17),interleukin-18(IL-18)and C reactive protein(CRP) in the process of coronary heart disease(CHD).Method:The levels of plasma interleukin-10(IL-10),interleukin-17(IL-17),interleukin-18(IL-18) and C reactive protein(CRP) in 160 patients(AMI 50,UA 68,SA 42) with CHD and 40 normal volunteers were determined by enzyme linked immunoadsorbent assay(ELISA).Result:The plasma levels of interleukin-10(IL-10),interleukin-17(IL-17),interleukin-18(IL-18) and C reactive protein(CRP) in patients with CHD were significantly higher than normal controls(P0.05).Conclusion:The findings suggest IL-10 is a protective factor of CHD,it can not hamper the genesis and development of CHD,meanwhile interleukin-17(IL-17),interleukin-18(IL-18) and Creactive protein(CRP) participate in the pathogenesis and progression of CHD.The plasma levels of these inflammatory factor will contribute to the diagnosis and monitoring of CHD.
Pathogenesis
Interleukin 1β
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