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At least 19 recordsLinked to original sources
PubMed1999

Interleukin-1 receptor-associated kinase and TRAF-6 mediate the transcriptional regulation of interleukin-2 by interleukin-1 via NFkappaB but unlike interleukin-1 are unable to stabilise interleukin-2 mRNA.

Interleukin-1 receptor-associated kinase, IRAK, has been shown to activate NFkappaB in response to interleukin-1. We have explored the involvement of IRAK in regulation of the interleukin-2 gene in the murine thymoma cell line EL4.NOB-1 by examining its effect on interleukin-2 promoter-linked reporter gene expression, interleukin-2 gene transcription and interleukin-2 protein production. Cells transfected with IRAK displayed high levels of phosphorylated IRAK, increased interleukin-2 promoter-linked reporter gene expression (which was dependent on NFkappaB) and interleukin-2 gene transcription. IRAK was unable, however, to increase interleukin-2 protein production. Overexpression of TRAF-6 induced similar responses and again failed to increase interleukin-2 protein production. A dominant negative TRAF-6 inhibited reporter gene expression and interleukin-2 protein production in response to both interleukin-1 and IRAK transfection. Interleukin-1 treatment and IRAK or TRAF-6 transfection increased interleukin-2 mRNA production. Only interleukin-1 treatment stabilised the induced transcripts with 50% being detectable at 20 h post induction. The interleukin-2 mRNA induced in IRAK- or TRAF-6-transfected cells was depleted by >90% at 6 h post induction. These data implicate IRAK and TRAF-6 in transcriptional regulation of interleukin-2 gene expression via NFkappaB, and provide direct evidence that IRAK lies upstream from TRAF-6. Neither IRAK nor TRAF-6 participates in stabilisation of interleukin-2 mRNA which is required for interleukin-2 protein production.

Animals↗
PubMed1992

Spontaneous in vivo gene transcription of interleukin-2, interleukin-3, interleukin-4, interleukin-6, interferon-gamma, interleukin-2 receptor (CD25) and proto-oncogene c-myc by rheumatoid synovial T lymphocytes.

Rheumatoid synovial T lymphocytes were investigated for the presence of mRNA for the cytokines interleukin-2, -3, -4, -6, interferon-gamma, the interleukin-2 receptor (CD25) and the proto-oncogene c-myc. The isolated RNAs were analysed by dot blot and Northern blot hybridization. Our results show that synovial T lymphocytes from patients with rheumatoid arthritis (n = 12) had spontaneous in vivo gene transcription of interleukin-2 (93%), interleukin-4 (67%), interleukin-6 (92%), interleukin-2 receptor (92%) and the proto-oncogene c-myc (67%). Only a few of the RA patients had synovial T cells with increased expression of mRNA for interleukin-3 (25%) and interferon-gamma (25%). The amounts of mRNA for the various cytokines and activation molecules produced by the rheumatoid synovial T lymphocytes were in most instances comparable to those of normal peripheral blood T lymphocytes activated in vitro by the mitogen phytohaemagglutinin. The data thus indicate that the synovial T lymphocytes are activated in vivo in the majority of rheumatoid arthritis patients.

Arthritis, Rheumatoid↗
PubMed2006

Aggressive non-Hodgkin's lymphoma: concomitant evaluation of interleukin-2, soluble interleukin-2 receptor, interleukin-4, interleukin-6, interleukin-10 and correlation with outcome.

The purpose of this study was to assess the prognostic value of a large panel of cytokines in aggressive non-Hodgkin's lymphoma (NHL) and to confront it to parameters of the International Prognostic Index (IPI). It investigated the concomitant determination of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) on a uniform population of 116 previously untreated patients. Commercially available enzyme-linked immunoassay kits were used for cytokines measurements. Results were correlated with complete remission (CR), overall survival (OS) and failure free survival (FFS). In univariate analysis, sIL-2R and IL-6 demonstrated prognostic significance for CR (p = 0.016 and p = 0.048), OS (p = 0.0011 and p = 0.0387) and FFS (p = 0.0001 and p = 0.0363), but multi-variate analysis failed to demonstrate an independent prognostic significance. In the intermediate group risk defined by IPI, patients presenting high level of sIL-2R or IL-6 demonstrated lower CR rate and survival than those with low level. In conclusion, sIL-2R and IL-6 serum levels are elevated in high grade NHL and are correlated to CR, OS and FFS, but this study did not support their independent prognostic value. However, sIL-2R and IL-6 measurements may improve risk assignment by IPI and allow a better prognostic evaluation of patients with intermediate prognosis NHL.

Adult↗
PubMed1990

Effects of interleukin-3 and interleukin-4 on the development of "connective tissue-type" mast cells: interleukin-3 supports their survival and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3.

We examined the effects of interleukin-3 (IL-3) and interleukin-4 (IL-4) on connective tissue-type mast cells (CTMC) purified from murine peritoneal cells. Although both factors failed to induce extensive proliferation of CTMC, they stimulated CTMC proliferation synergistically in a dose-dependent manner. Pretreatment of CTMC with IL-3 and/or IL-4 indicated that the sustained presence of both factors was required for the development of type 1 mast cell colonies. The delayed addition of IL-3 to cultures of purified CTMC with IL-4 induced no colony formation, while the delayed addition of IL-4 to cultures with IL-3, even on day 28 of culture, induced type 1 colony formation. In replating type 1 colonies induced by IL-3 and IL-4 to secondary cultures with IL-3 alone, few secondary colonies developed. However, the delayed addition of IL-4 to the secondary culture induced many type 1 colonies. The purified CTMC cultured with IL-3 retained the morphological and cytochemical characteristics of CTMC, as well as proliferative ability. These observations indicate that IL-3 supports the survival of CTMC in methylcellulose culture and that IL-4 triggers and supports CTMC proliferation synergistically with IL-3. The serum-free culture of purified CTMC and the culture of single CTMC demonstrated that the synergistic effect of IL-3 and IL-4 on colony growth and the surviving effect of IL-3 on CTMC require no influence from accessory cells or other humoral factors.

Animals↗
PubMed2005

Analysis of tumor necrosis factor-alpha, interleukin-6, interleukin-1beta, soluble tumor necrosis factor receptors I and II, interleukin-6 soluble receptor, interleukin-1 soluble receptor type II, interleukin-1 receptor antagonist, and protein in the synovial fluid of patients with temporomandibular joint disorders.

OBJECTIVE: To measure the levels of various cytokines, cytokine receptors, and cytokine antagonists in the synovial fluid of patients with temporomandibular disorders (TMD) and to determine the correlations among these expression levels. STUDY DESIGN: Synovial fluid was obtained from 55 patients with TMD and from 5 asymptomatic healthy volunteers as controls. The concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta, soluble tumor necrosis factor receptors I and II (sTNFR-I and sTNFR-II), IL-6 soluble receptor (IL-6sR), IL-1 soluble receptor type II, and IL-1 receptor antagonist were determined by enzyme-linked immunosorbent assay. RESULTS: The concentrations of TNF-alpha, IL-6, IL-1beta, sTNFR-I, and sTNFR-II were significantly higher in the synovial fluid of patients than in controls (P < .05). TNF-alpha level was positively correlated with those of IL-6, sTNFR-I, and sTNFR-II. In particular, there was a highly significant positive correlation between sTNFR-I and sTNFR-II. CONCLUSION: TNF and sTNFRs in the synovial fluid of patients with TMD may be important in the pathogenesis of these disorders.

Adult↗
PubMed1994

Interleukin 7 as interleukin 9 drives phytohemagglutinin-activated T cells through several cell cycles; no synergism between interleukin 7, interleukin 9 and interleukin 4.

The effects of the interleukins IL-7 and IL-9 on cell cycle progression were investigated by conventional [3H]thymidine incorporation and by the bivariate BrdU/Hoechst technique. Both IL-7 and IL-9 drive phytohemagglutinin-activated T cells through more than one cell cycle, but IL-7 was more potent on cell cycle progression than IL-9. Neither synergistic nor inhibitory effects were seen between various combinations of the lymphokines IL-7, IL-9 and IL-4 compared to each lymphokine alone. When T cells are activated with phytohemagglutinin for 3 days, all or most IL-4 responsive cells respond to IL-7 as well, whereas only a part of IL-7 responders are IL-4 responders. In contrast, when T cells are activated with phytohemagglutinin for 7 days, the quantitative data of the cell cycle distribution suggest that the population of IL-7 responders is at least an overlapping, if not a real subset of the population of the IL-4 responders.

Cell Cycle↗
PubMedDate not supplied

Interleukin-1 beta, interleukin-5, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in chronic sinusitis: response to systemic corticosteroids.

Recently, the role of various cytokines in the pathogenesis of chronic rhinosinusitis has come under investigation. Various studies have reported increased levels of interleukin-3, interleukin-4, interleukin-5, interleukin-13, and granulocyte macrophage-colony stimulating factor in the sinonasal mucosa of patients with chronic rhinosinusitis. The present study investigated the levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1 beta), interleukin-5 (IL-5), interleukin-6 (IL-6) interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha), in the sinonasal mucosa of patients with chronic rhinosinusitis, and evaluated the response of these cytokines to oral corticosteroids. Chronic rhinosinusitis subjects (n = 15) and control subjects (n = 9) underwent nasal endoscopy and biopsy of the sinonasal mucosa. Chronic rhinosinusitis subjects were subsequently treated with a 10-day tapering dose of prednisone followed by a second sinonasal endoscopic exam and biopsy. Mucosal biopsy specimens were immunostained for IL-1 beta, IL-5, IL-6, IL-8, and TNF-a. In chronic rhinosinusitis subjects, mucosal levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were significantly elevated when compared with control subjects, and levels of IL-5 demonstrated a strong trend toward elevation. In posttreatment chronic rhinosinusitis subjects, levels of IL-6 were significantly decreased when compared with pretreatment levels, and TNF-alpha levels demonstrated a significant trend toward reduction. These findings support the hypothesis that the inflammatory response in chronic rhinosinusitis is associated with elevated levels of pro-inflammatory cytokines, and suggest that oral corticosteroids may exert a beneficial effect by significantly reducing the levels of IL-6 and TNF-alpha.

Administration, Oral↗
PubMed1993

Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor.

Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.

Amyloid beta-Protein Precursor↗
PubMed1992

Cytokine responses to intraventricular injection of interleukin 2 into patients with leptomeningeal carcinomatosis: rapid induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and soluble interleukin 2 receptor (Mr 55,000 protein).

Interleukin 2 (IL-2) is a potent immunostimulant that causes the release of secondary cytokines and the production of lymphokine-activated killer cells. We investigated the cellular and cytokine responses to injection of recombinant human IL-2 into the human cerebrospinal fluid of 11 patients with metastatic tumors involving the spinal or cerebral leptomeninges. After initial intraventricular IL-2 administration (1.25 x 10(5) to 2 x 10(6) Cetus units/injection), cerebrospinal fluid samples were collected at intervals from 0 to 24 h. Enzyme-linked immunosorbent assay results indicated that IL-2 levels gradually decreased during the first 24 h, with an average t1/2 between 4 and 8 h. Induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and interleukin 2 receptor (p55) was also assessed by enzyme-linked immunosorbent assay. Tumor necrosis factor alpha and interleukin 6 levels peaked at 2 to 4 h and 4 to 6 h, with concentrations between 71 to 1,714 pg/ml and 942 to 10,500 pg/ml, respectively. Interleukin 1 beta, gamma-interferon, and soluble IL-2 receptor peaked later, during 6 to 12 h; the levels achieved were 234 pg/ml, 25 NIH units/ml, and 207 units/ml, respectively. All cytokine concentrations returned to near baseline between 12 and 24 h; however, the soluble IL-2 receptor levels remained elevated. Additional observations included a rapid influx of neutrophilic leukocytes, followed by a prolonged presence of lymphocytes. These data indicate a broad and complex potential of the immune response in the central nervous system, as well as further define the cytokine cascade in response to IL-2 alone.

Adenocarcinoma↗
PubMed1999

Elevated levels of interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6, soluble interleukin-6 receptor and vascular endothelial growth factor in serum and ascitic fluid of patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To investigate the possible role of vascular endothelial growth factor, interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6 and soluble interleukin-6 receptor in the pathogenesis of ovarian hyperstimulation syndrome. STUDY DESIGN: The study group consisted of 10 healthy women who developed severe ovarian hyperstimulation syndrome, group A (n=10), following ovarian stimulation by long GnRHa/hMG protocol for IVF. A control group B=10 patients underwent stimulation with the same protocol and did not develop OHSS. Blood and ascitic fluid samples were assayed for VEGF, IL-2, sIL-2Ralpha, IL-6 and sIL-6R by ELISA. RESULTS: The mean serum levels of IL-2, sIL-2Ralpha, IL-6, sIL-6R and VEGF in OHSS group were 297.5+/-190, 6588+/-5566, 40.6+/-16.6, 5280+/-3326 and 492+/-165 pg/ml as compared to 50.8+/-17.4, 1100+/-391.6, 8.5+/-3.5, 516+/-342 and 167+/-31.3 pg/ml in the control group, respectively, P<0.001. The mean ascitic fluid IL-2, sIL-2Ralpha, IL-6, sIL-6R and VEGF in the OHSS group were 282.5+/-191.5 pg/ml, 26020+/-13 995, 90.5+/-36, 14900+/-2789 and 660+/-359 pg/ml as compared to 32+/-14.8, 1206+/-429.4, 12.6+/-1.7, 614+/-240 and 151+/-20.5 pg/ml, respectively, P<0.001. CONCLUSIONS: The significantly high levels of VEGF in patients with severe OHSS suggest that VEGF is a major capillary permeability agent in OHSS. Elevated levels of IL-6 in serum and peritoneal fluid support the hypothesis that IL-6 may serve as a marker of OHSS. Although serum and ascitic fluid levels of IL-2 were elevated, accumulating evidence does not support a pivotal role for IL-2 in the pathogenesis of OHSS. However, it may have a peripheral role in mediating an increase in vascular permeability. Soluble IL-2Ralpha and sIL-6R may be considered to be involved in OHSS. However, the patho-physiologic mechanism is the subject of further investigations. Clinical application of VEGF-receptors in the management of OHSS is awaited with interest.

Adult↗
PubMed1992

Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist.

Interleukin 1 receptor antagonist (IL-1ra), a naturally occurring polypeptide with amino acid sequence homology to interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta), prevents Escherichia coli-induced shock and death. Both IL-1 and IL-1ra are produced by monocytes stimulated with lipopolysaccharide (LPS). Because interleukin 4 (IL-4) suppresses IL-1 production, we investigated whether IL-4 modulated IL-1ra synthesis in LPS-stimulated human peripheral blood mononuclear cells. IL-1 beta and IL-1ra were measured by specific RIAs. IL-4 alone (0.01-100 ng/ml) did not stimulate IL-1 beta synthesis but rather induced IL-1ra (4.82 +/- 0.94 ng/ml). LPS induced synthesis of both IL-1 beta (6.67 +/- 1.06 ng/ml) and IL-1ra (10.77 +/- 2.79 ng/ml). IL-4 suppressed LPS-induced IL-1 beta mRNA accumulation and synthesis. However, IL-4 acted synergistically with LPS in inducing IL-1ra. IL-4 enhanced LPS-induced IL-1ra mRNA accumulation 4-fold and IL-1ra protein synthesis nearly 2-fold. Moreover, IL-1ra mRNA levels were maximal after 6 hr of exposure to LPS but peaked within the first 3 hr in the presence of IL-4. IL-4 added as late as 12 hr after LPS stimulation still enhanced IL-1ra synthesis. In human peripheral blood mononuclear cells stimulated with IL-1 alpha, IL-4 markedly suppressed IL-1 beta production but enhanced IL-1ra synthesis greater than 2-fold. Because IL-4 favors synthesis of the natural antagonist IL-1ra over synthesis of the agonist IL-1, IL-4 may exert potent antiinflammatory effects on host responses to Gram-negative infections.

Gene Expression↗
PubMed1994

Interleukin-8 secretion and 15-lipoxygenase activity in rheumatoid arthritis: in vitro anti-inflammatory effects by interleukin-4 and interleukin-10, but not by interleukin-1 receptor antagonist protein.

We have examined the ability of interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-1 receptor antagonist protein (IL-1ra) to regulate spontaneous interleukin-8 (IL-8) production in cultured SF mononuclear cells (SFMC) from RA. Furthermore, we examined whether IL-4, IL-10, or IL-1ra could influence the production of the arachidonic acid products leukotriene B4 (LTB4), 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-hydroxy-eicosatetraenoic acid (15-HETE). IL-4 induced a maximal suppression of 75% in the IL-8 secretion in SFMC from 10.0 ng/ml down to 2.5 ng/ml after 24 h and from 17.2 ng/ml to 4.2 ng/ml after 72 h of culture. IL-10 induced a 55% inhibition of the IL-8 secretion at 24 h and a 40% inhibition at 72 h. IL-1ra did not change the spontaneous IL-8 secretion from rheumatoid SFMC. We also examined, whether addition of IL-4, IL-10 or IL-1ra was able to modulate formation of the arachidonic acid products LTB4, 12-HETE and 15-HETE in cultured SF cells, stimulated with the calcium ionophore A23187. 15-HETE was not detected in untreated cultures, nor in IL-10 or IL-1ra treated cultures. IL-4, however, stimulated the formation of the anti-inflammatory mediator; 15-HETE (23 ng/10(6) cells). These results suggest that IL-4 or IL-10, could have beneficial anti-inflammatory effects in RA.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2004

Interleukin-4 and interleukin-13 potentiate interleukin-1 induced secretion of interleukin-6 in human osteoblast-like cells.

Formation of interleukin-6 (IL-6) in osteoblasts and bone marrow stromal cells is believed to regulate osteoclast recruitment. The anti-inflammatory cytokines interleukin-4 and -13 (IL-4 and IL-13) stimulate IL-6 production in human osteoblasts. We investigated the relative potencies, and synergistic effects, between IL-4, IL-13 and interleukin-1 (IL-1) on IL-6 formation in human osteoblast-like cells. Isolated human osteoblast-like cells were incubated for 72 h in the presence of various concentrations of IL-4, IL-13 and IL-1, and IL-6 secretion was measured by ELISA. All cytokines stimulated the secretion of IL-6. The rank order of potency was IL-1>>IL-4>IL-13. There were no additive or synergistic effects between IL-4 and IL-13. However, co-stimulation with IL-1 and IL-4 resulted in a marked synergistic effect on IL-6 secretion. Co- stimulation with IL-1 and IL-13 gave a minor synergistic effect. In conclusion, IL-4/13 synergistically potentiates IL-1 induced secretion of IL-6 in human osteoblast-like cells.

Humans↗
PubMed1992

Inhibition of interleukin-1 (alpha and beta), interleukin-2 secretion and surface expression of interleukin-2 receptor (IL-2R) by a novel cytokine interleukin-1 receptor antagonist (IL-1ra).

IL-1 is a mediator of the acute inflammatory response and plays a key role in influencing growth and differentiation of immunocompetent lymphocytes. It can enhance transcription and secretion of the T-cell growth factor interleukin-2 (IL-2) and can stimulate the expression of membrane receptors for IL-2. However, the regulation and control of IL-1 activities are poorly understood. Recently an IL-1 inhibitor, interleukin-1 receptor antagonist (IL-1ra), has been described and cloned. This protein is a monokine originally found in the urine of febrile patients and in supernatants of human monocytes adhering to an IgG-coated surface, with an approximate molecular weight of 17 kDa, which is similar to IL-1 beta but having no IL-1-like activity and antagonizing IL-1 by binding to its cell surface receptor. These studies have examined some biological properties of hrIL-1ra, such as its effects on the secretion of IL-1 alpha or IL-1 beta and IL-2, the surface expression of IL-2R and DNA synthesis by peripheral blood mononuclear cells (PBMC). PBMC from normal volunteers were separated and used at a concentration of 2.5 x 10(6) cells/ml. The cells were pretreated for 2 h with hrIL-1ra (0.025-250 ng/ml), treated with LPS (10 ng/ml), and IL-1 alpha and IL-1 beta secretion were determined by an ELISA method. In addition the influence of hrIL-1ra (25 ng/ml) on IL-2 generation was determined. In another set of experiments, flow cytometric analysis with an anti-CD25 monoclonal antibody was determined on PHA-stimulated PBMC pretreated with hrIL-1ra (2 h) and cultured for 48 h. The inhibition by hrIL-1ra of IL-2R expression was dose-dependent and when hrIL-1ra was used at 250 ng/ml the IL-2R was completely abolished. Lymphocyte DNA synthesis calculated from the net uptake of [3H]-thymidine (3H-TdR) was also inhibited by hrIL-1ra (0.025-25 ng/ml). In this report we found that hrIL-1ra inhibits, in a dose-dependent manner, the secretion of IL-1 alpha, IL-1 beta, IL-2, the surface expression of IL-2R and 3H-TdR incorporation in PBMC in vitro. These data suggest a new biological activity of hrIL-1ra and further extend the immunomodulatory potential and significance of this new cytokine. The action of IL-1ra on modulating the synthesis of IL-1 may be of paramount importance in the regulation of these effects.

Concanavalin A↗
PubMed2000

Relationship between circulating interleukin-10 (IL-10) with interleukin-6 (IL-6) type cytokines (IL-6, interleukin-11 (IL-11), oncostatin M (OSM)) and soluble interleukin-6 (IL-6) receptor (sIL-6R) in patients with multiple myeloma.

We investigated the serum concentration of the interleukin-10 (IL-10), along with cytokines of interleukin-6 (IL-6) family (IL-6, IL-11 and oncostatin M - OSM), as well as soluble receptor for IL-6 (sIL-6R), in 121 patients with multiple myeloma (MM) and 28 healthy subjects. We studied the interactions between IL-10 and other cytokines, and the receptor. The correlation between IL-10 and some clinical and laboratory parameters associated with the disease activity were also analysed. The IL-10 was detectable in all patients with multiple myeloma and in all controls. The IL-10 concentration was significantly increased in myeloma patients compared with healthy persons (mean - 7.09 and 2.1 pg/ml, respectively) (p = 0.008). The level of IL-10 correlated positively with the advanced stage of disease estimated according to the Salmon and Durie classification (I versus III stage - p = 0.03). Higher values of IL-10 were found in patients with the light chain disease, hypercalcaemia, and correlated with the elevated concentrations of C-reactive protein (CRP). IL-6 was detected in 117 of the 121 patients and in all controls. The concentration of IL-6 was statistically increased in MM patients compared with control group (mean - 16.06 and 4.49 pg/ml, respectively) (p = 0.01). We found a positive correlation between IL-10 and IL-6 serum levels in MM patients. The relationship, expressed as Spearman's rank sum coefficient (rho = 0.249, p = 0.006) was significant. IL-11 was detected in 26 of the 121 MM patients and in 3 of the 28 healthy subjects at the mean concentration of 1.2 and 0.6 pg/ml respectively (p > 0.05). OSM was at detectable levels in 51 of the 121 patients and in only 4 of the 28 controls (mean - 3.84 and 0.1 pg/ml, p = 0. 002). The correlation between IL-10 and IL-11 levels in MM patients was not significant, but there was a strong statistical correlation between IL-10 and OSM concentrations (rho= 0.327, p = 0.0002). The serum concentration of sIL-6R was measurable in all patients and all controls (mean - 66.00 and 39.57 ng/ml respectively), but the difference between these groups was not significant. We found significant, positive correlation between the levels of IL-10 and sIL-6R (rho= 0.233, p = 0.01). In conclusion, we state that the serum concentrations of IL-10, IL-6, OSM and sIL-6R in MM patients may be a useful markers for the evaluation of the disease activity.

Adult↗
PubMed1992

Expression of interleukin-1 alpha, interleukin-1 beta, and an interleukin-1 receptor antagonist in human retinal pigment epithelial cells.

mRNA expression and protein production of interleukin-1 alpha, interleukin-1 beta and intracellular and secreted forms of an interleukin-1 receptor antagonist were measured in visually confluent monolayers of unstimulated cultured human retinal pigment epithelial cells and after cells were stimulated with recombinant cytokines. Using reverse transcription polymerase chain reaction, transcripts for interleukin-1 alpha and interleukin-1 beta were not detected in unstimulated cells from any of six donors whereas mRNA expression for both interleukin-1 alpha and interleukin-1 beta was readily induced in all six cell lines after cells were stimulated with recombinant IL-1 (alpha or beta), tumor necrosis factor alpha, or lipopolysaccharide. The combination of cycloheximide and recombinant interleukin-1 caused a 14-fold enhancement of interleukin-1 alpha and interleukin-1 beta mRNA expression above that observed after cells were stimulated with interleukin-1 alone. After stimulation by interleukin-1, cells produced intracellular interleukin-1 alpha protein, but did not secrete it into medium. In contrast, interleukin-1 beta protein was not detected in cell lysates or conditioned-medium after stimulation with interleukin-1. An intracellular interleukin-1 receptor antagonist was expressed constitutively by human retinal pigment epithelial cells; mRNA transcripts were enhanced in a dose and time dependent manner after cells were exposed to recombinant interleukin-1 or tumor necrosis factor alpha. In contrast, mRNA for a secreted form of the interleukin-1 receptor antagonist was not detected under basal conditions or after cells were stimulated by recombinant cytokines. Interleukin-1 receptor antagonist protein was found primarily in cell lysates; little interleukin-1 receptor antagonist protein was secreted by the cells. The presence of cell-associated interleukin-1 receptor antagonist was confirmed by immunocytochemistry. Levels of cell-associated IL-1 receptor antagonist protein were not significantly influenced by recombinant interleukin-1 or tumor necrosis factor alpha. Endogenous expression of interleukin-1 receptor antagonist may attenuate the effect of exogenous or endogenous interleukin-1, thus providing the RPE cell a means of maintaining interleukin-1 homeostasis in ocular inflammatory disease.

Cells, Cultured↗
PubMed1997

Role of interleukin-4 and interleukin-10 in murine collagen-induced arthritis. Protective effect of interleukin-4 and interleukin-10 treatment on cartilage destruction.

OBJECTIVE: To examine the role of endogenous interleukin-4 (IL-4) and interleukin-10 (IL-10) and the therapeutic effect of the addition of IL-4 and IL-10 in early and established murine collagen-induced arthritis (CIA). METHODS: Murine recombinant IL-4, IL-10, or the combination was given intraperitoneally twice daily from the day of arthritis onset up to 7-10 days of CIA in DBA/1 mice. Anti-IL-4, anti-IL-10, or both antibodies were given intraperitoneally before or after the onset of CIA. The effect of cytokine or anticytokine treatment was monitored visually by macroscopic scoring. Histology and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at the end of the treatment period. RESULTS: IL-4 alone did not provoke any effect, IL-10 slightly suppressed the arthritis, but a more pronounced amelioration was found with the combination. This cooperative effect was noted after early treatment but also occurred when the start of treatment was delayed until 1 week after onset. Apart from suppression of macroscopic signs of inflammation, combined treatment with IL-4/IL-10 also reduced cellular infiltrates in the synovial tissue and caused pronounced protection against cartilage destruction. Moreover, levels of mRNA for tumor necrosis factor alpha (TNF alpha) and IL-1 were highly suppressed both in the synovial tissue and in the articular cartilage. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) mRNA remained elevated, which suggests that the mechanism of protection may be related to suppressed production of TNF alpha and IL-1, with concomitant up-regulation of the IL-1Ra/IL-1 balance. However, accelerated onset of CIA and increased severity could be achieved with neutralizing anti-IL-10 antibodies. This expression could be further optimized with a combination of anti-IL-4 and anti-IL-10 antibodies, although anti-IL-4 alone was without effect. CONCLUSION: Our data are consistent with a dominant role of IL-10 in the natural suppression of arthritis expression, whereas combined treatment with IL-4 and IL-10 appears of potential therapeutic value, not only at the onset, but also in established arthritis.

Animals↗