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D L Kreutzer

Publications and source records attributed to D L Kreutzer.

At least 37 records · Page 2Linked to original sources
PubMed1997

Coexpression of interleukin-8 receptors in head and neck squamous cell carcinoma.

BACKGROUND: Interleukin 8 (IL-8) is an important cytokine involved in tumor growth and angiogenesis in a variety of malignancies. We hypothesize that IL-8 plays an important role in the cellular proliferation and angiogenesis seen in head and neck squamous cell carcinoma (HNSCC) and set out to identify its receptors, IL-8RA and IL-8RB. METHODS: Immunohistochemical analysis was performed on specimens from 38 HNSCC patients with stage I to IV disease and control tissues. RESULTS: All of cancer specimens demonstrated positive staining for IL-8RA. The IL-8RA staining of microvessel endothelial cells was seen in 51%. The IL-8RB pattern was similar to the IL-8RA pattern in that 97% of cancer sections demonstrated positive cancer cell staining, and 74% of the specimens demonstrated positive staining for microvessel endothelial cells. CONCLUSION: Our studies demonstrate that IL-8 receptors are expressed by cancer cells and microvessel endothelial cells in HNSCC, suggesting that IL-8 may act in an autocrine/paracrine fashion to stimulate cellular proliferation and angiogenesis.

Animals↗
PubMed1997

Vascular endothelial growth factor expression in head and neck squamous cell carcinoma.

BACKGROUND: Angiogenesis is an essential process required for growth and metastasis in cancer. In breast, gastric, and prostate cancer, vascular endothelial growth factor (VEGF) has been implicated in angiogenesis; however, little is known about VEGF in HNSCC. In this study, we hypothesize that VEGF is present in elevated levels in HNSCC and may therefore play a role in promoting angiogenesis. METHODS: We obtained tumor tissue from 63 HNSCC patients undergoing primary resection. All tissue samples were analyzed by immunohistochemistry (IHC) techniques for the presence and localization of VEGF; however, only 36 had sufficient amounts of tissue for quantitative analysis of VEGF by ELISA. Nine control specimens taken from patients undergoing uvulopalatopharyngoplasty were also analyzed. RESULTS: In all 63 of our patient samples we found VEGF to be present and localized to the cancer cells and endothelial cells. The poorly differentiated cancer cells stained more intensely in comparison with the well-differentiated ones. There was a 20-fold increase in the patient levels when compared with controls levels (P > or =0.05). Analysis by enzyme-linked immunosorbent assay revealed elevated mean levels of VEGF (241 +/- 326 pg/mg total protein [TP]) with a range of 2 to 1484 pg/mg TP. The control specimens had mean levels of 13 +/- 11 pg/mg TP and a range of 1 to 78 pg/mg TP. Patients who exhibited higher levels of VEGF tended to have a higher rate of disease recurrence (P < or =0.048) and shorter disease-free interval (P < or =0.05). CONCLUSIONS: The expression of VEGF in elevated levels in the HNSCC tumor microenvironment appears to be associated with more aggressive disease. Based on our results, VEGF may be an important angiogenic factor associated with cancer cells and endothelial cells in HNSCC. Further studies are needed to better define the role of VEGF in HNSCC and its role as a potential target for therapeutic intervention.

Adult↗
PubMed1997

Chemotactic factors released in culture by intact developing and healing skin lesions produced in rabbits by the irritant sulfur mustard.

Development, peak and healing lesions were induced in the skin of rabbits by topical applications (on different days) of the chemical irritant sulfur mustard (SM). Immediately after the rabbits were euthanized, the intact lesions were excised and organ-cultured for 17 to 20 hours. The culture fluids from early, peak and healing SM lesions all showed high chemotactic activity for both PMN and MN. This finding suggests that the PMN and MN, seen microscopically in tissue sections of the lesions, were entering continuously, even during the healing process. The chemotaxins identified were the eicosanoid LTB4, the chemokine IL-8, and proteases producing the complement fragment C5a. Other studies from our laboratory showed that the number of cells containing IL-1, IL-8, MCP-1, and GRO mRNAs was increased in SM lesions. Chemotactic activity was released by both live and dead (frozen and thawed) cell suspensions of PMN, MN, and fibroblasts, suggesting that these cells were major sources of the chemotaxins produced by the SM lesion explants. Explants of normal skin produced considerable chemotactic activity for MN, but not for PMN. Chemotactic activity for PMN, and the release of LTB4, IL-8 and proteases cleaving C5 to C5a, occurred only in explants infiltrated by leukocytes.

Animals↗
PubMed1997

Alterations in bone metabolism in children with inflammatory bowel disease: an in vitro study.

BACKGROUND: In patients with inflammatory bowel disease (IBD), accelerated bone loss and osteopenia have been found. Potential etiologies of these bone abnormalities have included malnutrition, poor calcium intake or absorption, and the use of corticosteroids. Recent studies have suggested that circulating pro-inflammatory cytokines, which are produced in inflamed bowel, can have a profound effect on bone metabolism, particularly bone resorption. Our aim was to characterize the effects of serum from subjects with IBD on bone metabolism in an in vitro bone culture system. METHODS: Organ cultures of fetal rat parietal bones were treated with sera from 9 subjects with Crohn's disease, 7 with ulcerative colitis, and 10 controls with functional bowel disease (age range of all subjects 7-16 years). Patients were also classified by disease activity, serum albumin level, erythrocyte sedimentation rate (ESR), and serum interleukin (IL) 6 levels. The effects of sera on bone formation and resorption were quantified. RESULTS: Compared with control serum, serum from patients with Crohn's disease significantly decreased bone dry weight (p < 0.01) and calcium content (p < 0.001) during 96 h of culture, while serum from ulcerative colitis patients had no effect. While no difference in collagen synthesis was noted between any of the three experimental groups, noncollagen protein synthesis was lower in the ulcerative colitis group than in the control group or those with Crohn's disease (p < 0.05). DNA content was similar in all groups. There was no significant effect of serum from any experimental group on bone resorption. There was no demonstrable relationship between clinical disease activity, ESR, or serum IL-6 levels and measures of bone metabolism. Histologic evaluation of cultured bone showed marked differences between control subjects and Crohn's disease patients, with the latter being characterized by disorganization of mineral and osteoid and morphologically abnormal osteoblasts. CONCLUSIONS: Serum from children with IBD has a significantly different effect than control serum on an in vitro model of bone metabolism. Our data suggest that circulating factors may affect osteoblasts and bone formation, leading to bone loss. Further work will be required to further characterize the nature of these factors and develop treatment strategies to minimize their effects.

Adolescent↗
PubMed1997

Activated eosinophils in esophagitis in children: a transmission electron microscopic study.

BACKGROUND: Esophagitis in infants and children is often characterized by eosinophilic inflammation. The underlying pathophysiologic mechanisms leading to this type of inflammation, and the role of eosinophils in the clinical expression of esophagitis, are unknown. The purpose of this study was to demonstrate the ultrastructural activation state of eosinophils in esophagitis in infants and children. METHODS: Standard transmission electron microscopy was used to examine endoscopic esophageal biopsy material from patients with and without esophagitis, as defined by standard histologic criteria. RESULTS: Twelve esophagitis and three control cases were studied. In patients with esophagitis, electron microscopy revealed numerous eosinophils throughout the mucosa and invariably demonstrated signs of activation, including inversion of core-to-matrix densities and lucency of granule core protein. Eosinophils in an activated state were seen in active diapedesis through vascular endothelium into the mucosa. Eosinophils were sometimes seen in proximity to lymphocytes. Biopsies of control patients did not demonstrate eosinophils. CONCLUSIONS: Eosinophils present in esophagitis are activated by electron microscopic criteria, and can been seen in an activated state entering into the mucosa. This suggests that eosinophils play an active role in the pathophysiology of this disorder, and that proinflammatory factors are present that selectively recruit and activate eosinophils in esophagitis in children.

Adolescent↗
PubMed1997

Murine model of interleukin-8-induced otitis media.

Interleukin-8 (IL-8), a potent inflammatory mediator that is thought to control leukocyte recruitment and activation during inflammatory reactions, has been implicated in a variety of inflammatory diseases. Recent studies in our laboratory have demonstrated the presence of IL-8 in chronically inflamed human middle ear effusions. These data have led us to hypothesize that IL-8 is responsible for the leukocyte recruitment seen in otitis media. Because the effect of IL-8 on the middle ear mucosa has not been investigated and therefore its role in middle ear inflammation is not known, we investigated the ability of IL-8 to directly induce inflammation in the murine middle ear. For these studies, ICR mice were used to test the hypothesis that IL-8 could directly induce inflammation in the middle ear. Murine middle ears received 8-mL transtympanic injections of human IL-8 (25 mg/mL) in saline, heat-killed Streptococcus pneumoniae (1 x 10(8)/mL), or normal saline. Temporal bones were removed at 1, 4, 8, 24, and 48 hours, decalcified, and processed for histologic examination. Noninjected murine temporal bones served as controls. Normal saline-injected ears demonstrated little to no change as compared with temporal bones from noninjected ears. IL-8-injected ears histologically demonstrated thickening of the epithelial layer and subepithelial space (SES), with inflammatory cell infiltration in the SES peaking at 4 to 8 hours and resolving by 48 hours. Bacteria-injected ears demonstrated findings similar to, although not as extensive as, those found in IL-8-injected ears (i.e., inflammatory reactions peaked at 8 to 24 hours and resolved by 72 hours). Our results demonstrate that IL-8 is a potent inducer of middle ear inflammation and support the concept that IL-8 may be one of the key cytokines responsible for the leukocyte accumulation and activation seen in otitis media.

Animals↗
PubMed1997

Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells.

PURPOSE: A growing body of literature supports the role of angiogenesis in the development and spread of a variety of human cancers including prostate cancer (Pca). Angiogenesis is controlled by chemical signals known as angiogenic factors (AF) however, little is known about angiogenesis factors in prostate cancer. We evaluated the in situ and in vitro expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, in archival prostate cancer specimens and prostate cancer cell cultures during unstimulated and cytokine stimulated conditions. METHODS: Ex-vivo studies involved immunohistochemical analysis for VEGF expression and distribution in 25 archival specimens including, prostate cancer, benign prostatic hyperplasia (BPH) and normal prostate tissue. In-vitro studies utilized prostate cancer cells (DU-145) grown in culture and stimulated with cytokines thought to induce VEGF (i.e. IL-1 alpha, IL-1 beta, TNF-alpha and TNF-beta). Cell culture supernatants were analyzed by ELISA for VEGF levels. RESULTS: Immunohistochemical studies demonstrated that in 20 of 25 specimens prostate cancers cells stained positively for VEGF. BPH and normal prostate cells displayed little staining for VEGF. DU-145 prostate cancer cells produced low levels of VEGF in unstimulated conditions. Induction of DU-145 cells with cytokines resulted in differential stimulation whereby TNF was a potent inducer of VEGF, and IL-1 produced lesser but statistically significant increases in VEGF expression. CONCLUSIONS: Our immunohistochemical results indicate that significant levels of VEGF are present in prostate cancer, but not in BPH or normal prostate cells in-vivo. In-vitro studies suggest that differential regulation of angiogenesis factor expression by IL-1 and TNF occurs in prostate cancer. Identifying the angiogenesis factors involved in prostate cancer growth and understanding their regulation will lead to the development of anti-angiogenic strategies useful for diagnostic studies and therapeutic interventions.

Cells, Cultured↗
PubMed1996

Interleukin-1 receptor antagonist in head and neck squamous cell carcinoma.

BACKGROUND: We hypothesized that in head and neck squamous cell carcinoma, the overexpression of protumorigenic interleukin-1 (IL-1) activity within the tumor tissue is a result of decreased expression of the specific antagonist or inhibitor (ie, IL-1 receptor antagonist) by the tumor cells. Ultimately, this local overexpression of IL-1 activity increases tumor growth and metastasis. DESIGN: To test our hypotheses, immunologic analysis for IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist was performed on histologic sections and tumor homogenates of human head and neck squamous cell carcinomas. SETTING: University teaching hospital. PATIENTS OR OTHER PARTICIPANTS: Normal and tumor specimens were obtained from patients undergoing surgical resections of the head and neck for benign and malignant disease. RESULTS: Immunohistochemical analysis demonstrated the presence of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist within tumor cells and inflammatory cells in the tumor stroma in 19 of 19 tumor specimens. Quantitatively, IL-1 alpha was present in 19 of 19 tumor specimens (1.97 +/- 0.46 ng/mg of total protein [mean +/- SD]) and 5 of 9 normal specimens (0.23 +/- 0.12 ng/mg of total protein). All specimens contained IL-1 beta in detectable quantities (1.60 +/- 0.29 ng/mg of total protein in tumor specimens and 0.189 +/- 0.04 ng/mg of total protein in normal specimens). All specimens contained IL-1 receptor antagonist (368.87 +/- 57.63 ng/mg of total protein in tumor specimens and 585.10 +/- 166.03 ng/mg of total protein in normal specimens). The mean total IL-1/IL-1 receptor antagonist ratio was 13.26 +/- 2.31 in patients with cancer compared with 0.997 +/- 0.26 in normal patients. CONCLUSIONS: The increased IL-1 index in the cancer state compared with the normal state reflects an imbalance of IL-1 and IL-1 receptor antagonist, which may contribute to unrestricted growth and metastasis of head and neck squamous cell carcinoma.

Aged↗
PubMed1996

Tissue factor expression in human leukemic cells.

Patients with acute leukemia are at increased risk for thrombotic and hemorrhagic complications, particularly those patients with acute promyelocytic leukemia (APL) undergoing induction chemotherapy. These serious complications have been attributed by some authors to the release of tissue factor (TF) procoagulant activity (PCA), particularly during cytotoxic chemotherapy. In previous studies of normal peripheral blood cells, only cells of the monocyte lineage have been found to express TF PCA. Therefore, several questions remain regarding the origin and characterization of the PCA in malignant leukemic cells, particularly those thought to be derived from granulocyte progenitor cells. We utilized a full-length cDNA probe, several monoclonal antibodies (MAbs) and a sensitive one-stage PCA assay to study the expression of TF in the human cell line, HL-60, in human peripheral blood monocytes/macrophages (Mo/Mø) and in highly purified populations of human polymorphonuclear leukocytes (PMN). In the HL-60 cells we detected low but significant levels of TF mRNA and TF antigen (TF:Ag). In unstimulated cells, coordinate increased levels of TF mRNA, TF:Ag and TF PCA expression were noted following phorbol-ester-induced macrophage differentiation of the cells, but a decreased level of TF mRNA with no change in the basal level of TF:Ag expression occurred following retinoic acid-induced granulocyte differentiation of this cell line. Long-term cultures of stimulated mature Mo/Mø demonstrated initial coordinate expression of TF mRNA, TF:Ag and TF PCA, but TF:Ag expression persisted even after 7 days (when TF PCA was undetectable). No TF PCA, TF:Ag or TF mRNA was demonstrated in highly purified populations of human PMN, regardless of culture conditions. Discordant expression of TF mRNA, TF:Ag and TF PCA in HL-60 cells suggests the possibility of novel, post-synthetic mechanisms for the regulation of TF PCA expression, which might be dependent on the phenotypic differentiation level of the cell. Such mechanisms (yet to be defined) might account for the ability of some leukemic cells, which frequently express characteristics of more than one cell line (e.g. monocytes and granulocytes), to express a TF gene product capable of activating blood coagulation.

Antibody Specificity↗
PubMed1996

Decreased expression of transforming growth factor beta receptors on head and neck squamous cell carcinoma tumor cells.

BACKGROUND: Transforming growth factor beta (TGF-beta) has antiproliferative effects on normal and neoplastic cells that express specific TGF-beta receptors. We hypothesize that diminished expression of TGF-beta and/or its receptors may contribute to the uncontrolled proliferation of head and neck squamous cell carcinoma (HNSCCA) cancer cells. METHODS: Using immunohistochemical techniques, we characterized the expression of TGF-beta isoforms and TGF-beta receptors, TGF-beta(RI) and TGF-beta(RII), in HNSCCA. Tumor production of TGF-beta was evaluated in culture supernatants from a cytokine-stimulated HNSCCA tumor line (HTB-43). RESULTS: All control specimens displayed strong cell-associated staining of TGF-beta as well as both receptors. Forty-seven of 47 cancer specimens exhibited positive staining for TGF-beta in the tumor matrix. Forty of the 47 cancer specimens demonstrated no expression of TGF-beta(RI), and 43 of the 47 expressed no TGF-beta(RII). Only interleukin 1 alpha (IL-1 alpha) and IL-1 beta induced significant TGF-beta expression from the HTB-43 cells. CONCLUSIONS: Decreased expression of TGF-beta receptors may play a significant role in the pathogenesis of HNSCCA by allowing uncontrolled cell proliferation.

Carcinoma, Squamous Cell↗
PubMed1996

In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease.

Expression of tissue factor (TF) in the endothelium has been observed only rarely in human disease and has been thought to be elaborated on the surface of vascular endothelial cells (VECs) in vitro as an artifact of tissue culture. Using monoclonal antibodies and a novel probe for functional TF, we have localized TF to the VECs (and tumor cells) within the tumors of seven patients with invasive breast cancer but not in the VECs (or tumor cells) of benign tumors from ten patients with fibrocystic disease of the breast. The potent procoagulant TF was shown to be a marker of the initiation of angiogenesis in human breast cancer. Further evidence that the TF was the demonstration of a similar distribution of cross-linked fibrin only in the VECs of the malignant tumors. We interpret these data as further support for the concept that tumor cells can activate nearby VECs and regulate blood vessel growth in vivo. Large clinical pathologic studies will be necessary to determine whether TF is a useful marker for the "switch" to the angiogenic phenotype" in human breast disease and/or correlates with the thromboembolic complications of breast cancer.

Breast Neoplasms↗
PubMed1996

Evidence for involvement of superantigens in human periodontal diseases: skewed expression of T cell receptor variable regions by gingival T cells.

Immunomodulation by periodontopathic bacteria has been implicated in the pathogenesis of inflammatory periodontal diseases. A novel class of microbial-derived T cell mitogens, referred to as superantigens, has recently been described. Superantigens are unique in that they induce a tremendous activation and expansion of specific subsets of T cells in an antigen-independent manner, thereby causing immune dysfunction. Subsets of superantigen-expanded T cells can be identified with reagents that discriminate among different families of the variable domains of the T cell antigen receptor beta-chain (V beta). Since superantigens expand one or a few of these T cell antigen receptor V beta families, T cell subsets that have been expanded by superantigens have restricted expression of one or a few V beta families. In the present study, we investigated the presence of putative superantigen-stimulated T cells in periodontitis sites, utilizing a panel monoclonal antibodies to T cell antigen receptor V beta families. Leukocytes were isolated from gingival tissues obtained from 8 periodontitis and 4 non-periodontitis patients by collagenase digestion. Three-color flow cytometric analysis of these gingival cells demonstrated that in most periodontitis patients examined, patterns of V beta expression among T cells are characteristic of superantigen stimulation, i.e., there is an elevation in the proportion of one or a few V beta families. Specifically, these analyses revealed that T cell subsets expressing V beta 5a and V beta 5b, V beta 6, V beta 8 and V beta 12 were each elevated greater than 2 standard deviations in at least one periodontitis patient compared with the mean of the non-periodontitis subjects. In some periodontitis patients, a less marked elevation of T cells that express V beta 3, V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12, and V beta 13 was noted (greater than 1 standard deviation higher than the mean of the V beta families in non-periodontics subjects). Interestingly, V beta 8+ T cells were elevated to some degree in all periodontitis patients examined. In contrast, T cells expressing V beta 2, V beta 17 and V beta 19 were not significantly different in any of the subjects studied. In most periodontitis but not non-periodontitis patients, up to 50% of all gingival T cells expressed one or a few T cell antigen receptor V beta families, suggesting that superantigens constitute a major pathway of T cell activation and expansion. Hence, our data support the hypothesis that a large proportion of T cells in periodontitis sites have been stimulated and expanded by superantigens, presumably produced by periodontitis-associated bacteria.

Adult↗
PubMed1995

Fibrin activation of vascular endothelial cells. Induction of IL-8 expression.

Fibrin deposition and leukocyte accumulation are classic histopathologic hallmarks of acute and chronic inflammation. Although both of these processes are common to inflammatory processes, surprisingly little is known about the interrelationship between fibrin deposition and leukocyte accumulation. We hypothesized that: 1) fibrin can regulate inflammation by directly inducing leukocyte chemotactic factor (LCF) expression from vascular endothelial cells (VEC), and 2) this fibrin-induced VEC expression of LCF would enhance leukocyte recruitment seen in acute and chronic inflammation. To test this hypothesis, we developed an in vitro model system of in situ polymerization of fibrin on isolated bovine pulmonary artery endothelial cells in culture. In the initial phase of our studies, we found that fibrin induced a time- and dose-dependent expression of leukocyte migration activity from VEC. Checkerboard analysis demonstrated that the leukocyte migration activity present in the fibrin-stimulated VEC culture supernatant was truly chemotactic in nature. In an effort to begin to characterize this chemotactic activity, we demonstrated that this fibrin-induced LCF activity was 1) protein dependent, 2) not derived from fibrin(ogen), and 3) had an apparent m.w. of 6 to 12 kDa. Our further studies demonstrated that fibrin was a potent stimulus for IL-8 Ag expression from the VEC. Thus, these studies clearly demonstrate that fibrin has the capability to induce leukocyte chemotactic activity in general, and IL-8 activity specifically, from VEC. These studies support our hypothesis that fibrin is an important activator of vascular endothelial cells in vivo.

Animals↗
PubMed1995

Interleukin-8 expression by head and neck squamous cell carcinoma.

OBJECTIVE: To test the hypothesis that interleukin-8 (IL-8) is produced by human head and neck squamous cell carcinomas (HNSCCAs) and may therefore be a possible mediator for lymphocyte recruitment and neovascularization by these tumors. METHODS: Nine fresh samples of HNSCCA were analyzed for expression of IL-8 antigen using radioimmunoassay and immunohistochemical staining techniques. Also, four short-term primary cultures of HNSCCA and two continuous HNSCCA cell lines were then analyzed for production of IL-8 expression under both baseline conditions and following stimulation with other cytokines. RESULTS: The IL-8 antigen was detected in all fresh tumor homogenates by radioimmunoassay (5.58 to 331.69 ng of IL-8 per gram of tissue), and immunohistochemical results localized staining predominantly within the tumor cells. Primary cultures of HNSCCA and continuous HNSCCA cell lines produced only low levels of IL-8 (0.04 to 4.49 ng of IL-8 per 10(6) cells) under baseline (unstimulated) conditions. Stimulation of both primary cultures and cell lines with interleukin-1 and tumor necrosis factor induced significant increases in IL-8 antigen, while other cytokines failed to induce a significant increase. CONCLUSIONS: This study demonstrates that IL-8 antigen is expressed by HNSCCA in vivo, and that cultured HNSCCA in vitro can be stimulated to express IL-8 antigen by both interleukin-1 and tumor necrosis factor. Local production of IL-8 by HNSCCA cells, and its regulation by other cytokines, may be important in both the lymphocyte recruitment and tumor neovascularization seen in HNSCCA, and may thus ultimately affect the natural history of the disease.

Carcinoma, Squamous Cell↗
PubMed1995

Enhanced tumor cell expression of tumor necrosis factor receptors in head and neck squamous cell carcinoma.

BACKGROUND: To determine if tumor necrosis factor (TNF) receptors are upregulated in tumor cells, we measured the distribution and levels of TNF-alpha and TNF-beta, and TNF receptors RI and RII, in head and neck squamous cell carcinoma (HNSCC) tumor specimens and normal control specimens. METHODS: HNSCC and control tissue specimens were analyzed qualitatively using immunohistochemistry and quantitatively using immunoassays. RESULTS: Immunohistochemical analysis revealed that TNF-alpha, TNF-beta, TNF RI, and TNF RII antigens were associated predominately with tumor cells in the tissue. Quantitative analysis of TNF factors and receptors in tissue homogenates (mean levels +/- standard error of the mean, in pg/mg of total protein) indicated that: (1) TNF-alpha levels in cancer patients were not statistically different from levels in normal tissues (7.27 +/- 0.91 versus 4.62 +/- 1.33, respectively, P < 0.11); (2) TNF-beta levels in cancer patients were one third of those in normal tissue (5.07 +/- 1.83 versus 16.06 +/- 3.26, respectively, P < 0.01); and (3) both TNF RI and TNF RII levels were consistently elevated two- to four-fold in the cancer tissue when compared to normal tissue levels (1,228.72 +/- 125.67 versus 650.33 +/- 187.70, P < 0.01; and 823.39 +/- 95.90 versus 230.03 +/- 153.01, P < 0.002, respectively). CONCLUSIONS: In HNSCC, enhanced expression of TNF receptors on the cancer cells occurs and is likely to contribute to the regulation of TNF and its activation of tumor cells within the tumor microenvironment; targeting these receptors in cancer cells may provide a new approach to controlling tumor growth and metastasis.

Adult↗
PubMed1995

Relationship of interleukin-1 receptor antagonist to mucosal inflammation in inflammatory bowel disease.

Previous work has suggested that the interleukin-1 (IL-1) receptor antagonist, IL-1ra, may regulate mucosal inflammation in inflammatory bowel disease. The present study assessed the relationship of mucosal IL-1ra levels to histologic severity of inflammation and the related proinflammatory cytokines IL-1 beta and IL-6 in children with inflammatory bowel disease. Colonic biopsy specimens from 29 patients with ulcerative colitis, 27 with Crohn's disease, and 24 noninflammatory control subjects were assayed for IL-1ra, IL-1 beta, and IL-6 by enzyme-linked immunosorbent assay. Histologic activity was graded as none, mild, moderate, or severe. Mucosal IL-1 beta levels, but not IL-1ra levels, were significantly elevated in moderate/severely inflamed biopsies from patients with either ulcerative colitis (p < 0.01) or Crohn's disease (p < 0.001) compared with those with none/mild inflammation. The mucosal molar ratio of IL-1ra/IL-1 beta was significantly lower for moderate/severe inflammation compared with none/mild inflammation for patients with ulcerative colitis (p < 0.05) and Crohn's disease (p < 0.01). The mucosal IL-1ra/IL-1 beta ratio was similar in controls to none/mild inflamed biopsies from subjects with either ulcerative colitis or Crohn's disease. Our observations suggest that increasing mucosal inflammation in inflammatory bowel disease in children is associated with a decrease in the "normal" effective IL-1ra/IL-1 beta ratio in which IL-1ra predominates. The importance of this abnormality to the pathogenesis of inflammatory bowel disease awaits further study.

Adolescent↗
PubMed1995

Localization of interleukin-8 in human gingival tissues.

Periodontitis and gingivitis are chronic inflammatory diseases of the periodontium and adjacent tissues. This site-specific inflammation is characterized by a local infiltration of polymorphonuclear leukocytes and T lymphocytes. Interleukin-8 is a low molecular-weight cytokine that is thought to be responsible for the induction and maintenance of localized inflammation. We hypothesized that locally produced interleukin-8 plays a central role in chronic inflammation of periodontitis by regulating the recruitment and activation of leukocytes in the gingival tissues. To test this hypothesis, we determined whether the interleukin-8 antigen is present locally and is cell-associated. Inflamed and control tissues were analyzed: 1) for the interleukin-8 antigen; 2) by molecular weight; 3) for location; and 4) for the messenger RNA (mRNA) of interleukin-8. The conclusions from these data were that: 1) interleukin-8 antigen and mRNA was elevated in chronically inflamed gingiva; and 2) the major interleukin-8 antigen was detected only in the epithelial cell layer. These results support that interleukin-8 may play a crucial role in the recruitment and activation of neutrophils and T lymphocytes in periodontitis.

Adolescent↗