Stem Cell Factor (SCF) and Interleukin 3 (IL-3) in the Sera of Patients with Colorectal Cancer

For a long time markers that can detect a malignant cell transformation as early as possible have been sought. Substances which have been discovered are known as tumor markers. Stem cell factor (SCF) and interleukin 3 (IL-3) are members of a group of glycoprotein growth factors called hematopoietic cytokines (HCs). These factors take part in the regulation of developmental processes of hematopoietic progenitor cells and it was proved that HCs can be produced by different cancer cells, including colorectal cancer. The aim of this study was to investigate a potential role for SCF and IL-3 as tumor markers for colorectal cancer. We compared the serum levels of SCF and IL-3 in colorectal cancer patients with those in healthy subjects (control group) and commonly accepted tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). We defined the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and receiver-operating characteristics (ROC) curve of tested substances. SCF and IL-3 were determined using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19-9 were measured by microparticle enzyme immunoassay. The serum levels of HCs and tumor markers were investigated in 75 patients with colorectal cancer and in 40 healthy subjects. There were significant differences in the level of circulating SCF and IL-3 in the colorectal cancer patients compared to the control group. Moreover, the diagnostic sensitivity of SCF was higher than the sensitivity of CEA and CA 19-9. The SCF area under the ROC curve was larger than the IL-3 area but smaller than the CEA and CA 19-9 areas. The diagnostic specificities of cytokines were lower than those of tumor markers, but the combined use of cytokines and tumor markers increased the diagnostic values. The highest values of diagnostic parameters were observed for the combined use of SCF and CA 19-9. These results suggest a potential role for SCF and IL-3 as tumor markers for colorectal cancer, especially in combination with CEA or CA 19-9.     

IL-1和IL-6与急性胰腺炎相关性的实验研究

目的探讨血清IL-1和IL-6含量与急性胰腺炎病变程度的相关性。方法Wistar大鼠120只随机分为3组,每组40只,正常对照组腹腔注射生理盐水,急性胰腺炎组腹腔注射L-arginine500mg/100g,每小时1次,共3次,IL-10干预组在诱导胰腺炎模型后的2、5、8h腹腔注射IL-10各10000u。各组于造模后的4、12、24、36h分批处死大鼠,进行组织病理评分、全自化生化分析仪检测CRP、ELISA法检测IL-1和IL-6浓度。结果急性胰腺炎组病理评分、CRP、IL-1及IL-6含量均显著高于正常对照组,IL-10干预组各项指标均较急性胰腺炎组显著下降,急性胰腺炎组中IL-1、IL-6与病理评分及CRP存在正相关。结论大剂量腹腔L-arginine诱导的重症急性胰腺炎大鼠中,血清IL-1、IL-6及CRP显著升高,应用IL-10可显著减轻胰腺病变程度,IL-1、IL-6浓度与胰腺病变正相关。     

Interleukin (IL)-4 and IL-13 inhibit the differentiation of murine osteoblastic MC3T3-E1 cells

Interleukin-4 (IL-4) inhibits the spontaneous and stimulated bone resorption resulting from the inhibition of osteoclast formation, as well as osteoclastic activity. Since IL-13 shares some biological properties with IL-4, it was recently reported that IL-13 inhibits bone resorption. The present study was designed to determine the effects of murine IL-4 (IL-4) and murine IL-13 (IL-13) on the murine osteoblastic cell line MC3T3-E1. IL-4 and IL-13 stimulated 3H-thymidine incorporation in the MC3T3-E1 cells and its proliferation in dose dependent manners. A spontaneous increase in alkaline phosphatase (ALP) activity in the cells after plating was inhibited by IL-4 or IL-13, and both cytokines blunted an increase in ALP activity by human parathyroid hormone (PTH) (1-34). PTH-stimulated cyclic AMP (cAMP) production was inhibited by pretreatment with IL-4 and IL-13 for 48 hr in dose dependent manners. Pretreatment with IL-4 and IL-13 for 48 hr caused a decrease in PTH-induced cAMP production at any stimulatory concentration. However, the effective dose (ED50) was unchanged by the pretreatment with these cytokines. Pretreatment with IL-4 and IL-13 did not modulate cAMP generation by forskolin. In contrast, cAMP generation by PGE2 is greater in the cells treated with the cytokines compared to those without the cytokines. These results indicate that IL-4 and IL-13 act on MC3T3-E1 cells in the same manner, stimulating cell proliferation, but inhibiting cell differentiation. The inhibition of osteoblast differentiation by IL-4 and IL-13 may be associated with a decrease in PTH actions on osteoblasts.     

Clinical Significance of Interleukin 33 (IL-33) in Patients with Eosinophilic Pneumonia

Background: Interleukin 33 (IL-33) works as a functional mediator in allergic disease by enhancing the activity of eosinophils and inducing expression of T helper 2 (Th2)-associated cytokines. However, the role of IL-33 in pulmonary eosinophilia has not been elucidated. We investigated the levels of IL-33 in eosinophilic pneumonia (EP) together with associated cytokines, and discussed the clinical significance of IL-33 in EP.Methods: Sera and bronchoalveolar lavage fluid (BALF) were obtained from 16 patients with EP, including acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP). Twelve patients with acute respiratory distress syndrome (ARDS) were also included for comparison. The concentration of IL-33 and Th2 cytokines (IL-4, IL-5, IL-13) were measured by enzyme-linked immunosorbent assay (ELISA).Results: The concentration of serum IL-33 was significantly higher in patients with AEP than in CEP. In CEP, only patients with atopic factors showed mild increase of serum IL-33. The concentration of BALF IL-33 was also significantly elevated in AEP, however, it remained quite low in CEP. Among Th2 cytokines, IL-5 was significantly increased in both serum and BALF in AEP, and the level of IL-5 was positively correlated with that of IL-33. ARDS showed no increase of serum and BALF IL-33.Conclusions: The remarkable increase of BALF IL-33 in AEP indicated the local production of IL-33 in lungs. IL-33 is considered to be a local key molecule for triggering pulmonary eosinophilia, together with IL-5. BALF IL-33 appears to be a useful marker for discriminating AEP from CEP and ARDS.     

Interleukin (IL)-13 and IL-4 Are Potent Inhibitors of IL-8 Secretion by Human Intestinal Epithelial Cells

Intestinal epithelial cells are able to producesoluble mediators that initiate or amplify inflammatoryevents in the intestinal mucosa. Interleukin (IL)-8 issuggested to be a cytokine playing a major role during the acute and chronic processes ininflammatory bowel disease (IBD). TH-2 cytokines havebeen described as down-regulating the inflammatoryresponse. We analyzed the effects of IL-10, IL-13, and IL-4 on IL-8 secretion in intestinalepithelial cells. The human colonic epithelial cell lineCaco-2 and freshly isolated intestinal epithelial cellswere used. Cells were stimulated with IL-1beta after treatment with TH-2 cytokines. Levels of IL-8were determined by employing enzyme-linked immunosorbentassay (ELISA). Stimulation with IL-1beta results in atime-dependent IL-8 secretion. The addition of IL-4 and IL-13, but not IL-10, to activatedepithelial cells resulted in a strong decrease in IL-8secretion. Maximal inhibition required that TH-2cytokines be added up to 60 min before or simultaneous with stimulatory agents. We present novelfindings that IL-4 and IL-13 strongly down-regulate IL-8secretion from intestinal epithelial cells. Amicroenvironment containing high concentrations of IL-4and IL-13 may alter the recruitment of immune cellsto enterocytes at least partly by inhibiting IL-8production. This inhibition might diminish the severityof the intestinal inflammatory response and, thus reduce clinical disease activity.     

Interleukin (IL)-4, IL-10 and IL-12 profile in serum of patients with alveolar echinococcosis.

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E.m.), provokes a characteristic immune response. Based mainly on in vitro studies, Th2 dominated immunity is associated with increased susceptibility to disease, while Th1 cell activation is assumed to induce protective immunity. We investigated serum levels of interleukin (IL)4, IL-10, and IL-12 in 40 AE patients and 20 controls to assess Th1/Th2 cell activation in vivo. Significantly higher levels of IL-10 were found in AE patients (P = 0.003) than in controls, with a tendency to higher concentrations in progressive cases. In contrast, IL-4 was only measurable in a minority of patients and controls. IL-12 levels (measured with an ELISA that detects both the p35/p40 heterodimer and free p40) were comparable between AE patients and controls and showed a similar distribution pattern to IL-10 with regard to disease progression. By using an IL-12-ELISA specific for the heterodimer, only minute amounts of IL-12 were detectable in merely a minority of samples. In conclusion, our data are suggestive of Th2 dominated immune response in AE in vivo.     

Interleukin (IL)-17 promotes macrophages to produce IL-8, IL-6 and tumour necrosis factor-alpha in aplastic anaemia

Aplastic anaemia (AA) is thought to be an autoimmune-mediated disease with active destruction of haematopoietic cells through a T helper type 1 (Th1) cell response. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies indicate that IL-17 might be an essential effector cytokine in the T-cell mediated autoimmune process. It can drive the production of tumour necrosis factor-α (TNF-α), IL-1 β, IL-6 and IL-8 by a variety of cells. The present study investigated the genetic and protein expression of IL-17 in patients with AA. The effect of IL-17 on IL-6 and IL-8 production by macrophages was also studied. AA patients showed an elevated expression of IL17A mRNA in bone marrow mononuclear cells and peripheral blood mononuclear cells. Higher IL-17 in bone marrow and peripheral blood plasma was also observed in AA patients compared with normal controls. IL-17 induced the production of IL-6 and IL-8 by macrophages both from patients with AA and normal controls. IL-17 stimulation also resulted in the production of TNF-α. These results suggested that elevated expression of IL-17 and IL-17-induced IL-6, IL-8 and TNF-α may be involved in the mechanisms of AA.     

Interleukin (IL)-2 and IL-3 induce distinct but overlapping responses in murine IL-3-dependent 32D cells transduced with human IL-2 receptor beta chain: involvement of tyrosine kinase(s) other than p56lck.

We have established IL-3-dependent 32D myeloid progenitor cells stably expressing the human IL-2 receptor beta chain (IL-2R beta). Whereas parental 32D cells proliferated only in response to IL-3, the transduced cells also proliferated in response to IL-2. Transduced cells expressed high- and intermediate-affinity IL-2Rs, resulting from expression of human IL-2R beta and murine IL-2R alpha chain (IL-2R alpha). IL-2 induced phenotypic changes not induced by IL-3, including the upregulated expression of endogenous murine IL-2R alpha and IL-2R beta and an increase in cell size. Therefore, the transduced IL-2R beta was not merely coupling with the IL-3 signaling pathway. IL-3 augmented several IL-2-induced responses including the up-regulation of IL-2R alpha. Both IL-2- and IL-3-induced proliferation and IL-2 induced IL-2R alpha expression were inhibited by the tyrosine kinase inhibitor herbimycin A. Thus, both IL-2- and IL-3-mediated effects required tyrosine kinase activity. The identity of the tyrosine kinase(s) mediating the IL-2 signals in these cells is not known but cannot be p56lck, a tyrosine kinase found in T cells, since 32D-IL-2R beta cells do not express p56lck.     

溃疡性结肠炎的白细胞介素(IL)-1β、IL-1受体拮抗剂、IL-4基因多态性

目的研究溃疡性结肠炎(UC)病人的白细胞介素(IL)-1β、IL-1受体拮抗剂(IL-1RA)、IL-4基因多态性,并分析其与抗中性粒细胞胞质抗体(ANCA)及临床分型的关系.方法用PCR-限制性片段长度多态性方法和序列特异性引物-PCR方法分别对81例UC病人和114例健康者进行IL-1β和IL-1RA、IL-4基因多态性分析.结果 UC组IL-4 的RP2基因频率明显高于对照组(29.0% 对11.8%,P=0.000 02),而对照组RP1基因频率明显高于UC组(88.2% 对71.0%,P=0.000 02),UC组RP1.2、RP2.2基因型的优势比值分别为2.71 (95%CI, 1.39～5.31),9.04 (95%CI, 1.05～203.29);2组IL-1β、IL-1RA各基因频率比较差异均无显著性 (P＞0.05);ANCA(+)组和ANCA(-)组UC病人IL-4的 RP1、RP2基因频率显著不同,差异有显著性 (P值均<0.05).结论中国汉族UC病人与IL-4内含子3的基因多态性相关联,UC病人IL-4 RP1基因频率明显降低,而RP2基因频率明显增加,与正常人的差异发生在 ANCA(+) UC病人;中国汉族UC病人与IL-1β、IL-1RA基因多态性无关联.     

Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella in humans

Patients with inherited deficiency of the interleukin (IL)-12/IL-23-interferon (IFN)- gamma axis show increased susceptibility to invasive disease caused by the intramacrophage pathogens salmonellae and mycobacteria. We analyzed data on 154 patients with such deficiency. Significantly more patients with IL-12/IL-23-component deficiency had a history of salmonella disease than did those with IFN- gamma -component deficiency. Salmonella disease was typically severe, extraintestinal, and caused by nontyphoidal serovars. These findings strongly suggest that IL-12/IL-23 is a key cytokine for immunity against salmonella in humans and that IL-12/IL-23 mediates this protective effect partly through IFN- gamma -independent pathways. Investigation of the IL-12/IL-23-IFN- gamma axis should be considered in patients with invasive salmonella disease.     

Interleukin 16 (IL-16) in asthma and allergic rhinitis. A comparison between upper and lower airways

Asthma is a chronic inflammatory disease of bronchial mucosa, in which mast cells, eosinophils and activated T cells are of considerable importance. The increased chemotactic activity for T cells in patients with asthma is mainly attributable to IL-16. A strong association between asthma and allergic rhinitis exists from a clinical and epidemiologic standpoint of view. Although it is clear that the condition of the upper airways has impact on the lower airway physiology, the precise mechanisms underlying this relation are far from being resolved. This work was assessed the role of interleukin 16 (IL-16) in bronchoalveolar lavage (BAL) fluid in both diseases using quantitative sandwich enzyme immuno-assay, and the effect on ventilatory function. The results showed abnormally increased levels of IL-16 (294.4 +/- 15.24 pg/ml), serum eosinophils with absolute count (510.0 +/- 93.57, P>0.05), and total serum IgE (287.9 +/- 61.22 IU/ml) using ELFA in patients of combined asthma and rhinitis, than in each of them alone. There was reduction in FEV1 (forced expiratory volume in the first second) in the same group (81.6 +/- 2.01%). There was a negative correlation between BAL IL-16 and FEV1. In conclusion IL-16 may be considered as a marker of severity of airway inflammation.     

Interleukin 1 (IL 1)

Interleukin 1 is an essential factor of macrophage dependent T cell activation and has a large quantity of other biological activities. This paper gives a review of present knowledge of Interleukin 1. In addition to biochemical properties, the IL 1 production and IL 1 activities, methods for determining of IL 1 and inhibitory factors of IL 1 induced T cell proliferation are described.     

Interleukin (IL)-1beta regulation of IL-1beta and IL-1 receptor antagonist expression in cultured human endometrial stromal cells

The interleukin (IL)-1 system is a major regulator of local cellular interactions during embryonic implantation. Because IL-1beta and IL receptor antagonist (IL-1ra) are both expressed in human endometrium, we hypothesized that an appropriate ratio of IL-1beta to IL-1ra might favor the process of embryo implantation. Therefore, we investigated IL-1 regulation of the quantitative ratio of IL-1beta/IL-1ra messenger RNA (mRNA) expression in human endometrial stromal cells using quantitative competitive PCR, as well as intracellular protein expression after stromal cell solubilization. Confluent stromal cell cultures were stimulated with human IL-1beta (0-1000 IU/mL) for 24 h. After 24 h, total RNA was extracted, reverse transcribed, and coamplified by PCR with a defined amount of internal standard. The quantitative ratio was determined by the density of target to the internal standard. After culture with IL-1beta for 24 and 48 h, stromal cells were solubilized, and the intracellular protein levels of IL-1beta and IL-1ra were measured by enzyme-linked immunosorbent assay. The IL-1beta and IL-1ra mRNA were both up-regulated, and IL-1R tI mRNA was down-regulated, by IL-1beta in a dose-dependent manner. The quantitative ratio of IL-1beta to IL-1ra mRNA was constant with the presence of increasing concentrations of IL-1beta (1-1000 IU/mL). IL-1beta and IL-1ra protein was not detected in conditioned media of cultures before addition of IL-1beta. IL-1beta and IL-1ra protein levels increased with increasing amounts of IL-1beta after solubilization of stromal cells. The IL-1beta was detectable after 12 h of culture, in comparison with IL-1ra, which was detectable after 24 h of IL-1beta stimulation. These results suggest that IL-1 may play a crucial role in embryo-maternal interaction by regulating stromal cell expression of IL-1beta and IL-1ra, resulting in an appropriate ratio during the process of embryonic implantation.     

Polymorphisms in Interleukin-1B (IL-1B) and Interleukin 1 Receptor Antagonist (IL-1RN) Genes Associate with Gastric Cancer Risk in the Chinese Population

Background  

Gastric cancer is one of the most common malignancies afflicting the Chinese population. Polymorphisms in interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) genes have been associated with increased gastric cancer risk.