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Biomedical subjects

I Kirman

Publications and source records attributed to I Kirman.

29 records · Page 2Linked to original sources
PubMed1997

Expression of common gamma chain on peripheral blood mononuclear cells in Crohn's disease.

Mononuclear cell proliferative response to IL-2 and functional response to IL-4 is disturbed in IBD. The aim of the present study was to verify whether altered expression of the common gamma chain (gamma c) might contribute to this abnormality. The gamma c expression on peripheral blood mononuclear cells was analyzed by flow cytometry using a monoclonal antibody to gamma c. IL-4 binding in association with gamma c expression was assessed using biotinylated IL-4 in two-color flow cytometry. Mean fluorescence of gamma c expression was significantly decreased in active CD patients as compared to inactive CD and healthy controls (P < 0.05). Cell activation as a possible reason for gamma c down-regulation was confirmed using the in vitro stimulated donor cells. In the same system it was shown that down-regulation of gamma c is accompanied by decreased numbers of IL-4 binding cells. In conclusion, a decreased expression of the gamma c on peripheral blood mononuclear cells from CD patients with active disease might have an important pathogenetic significance in this chronic intestinal disorder.

Adult↗
PubMed1997

Peritoneal lavage reduces lipopolysaccharide-induced elevation of serum TNF-alpha and IL-6 mortality in mice.

The contribution of peritoneal cells to lipopolysaccharide (LPS)-induced elevation of serum TNF-alpha and IL-6 levels and mortality has been studied. Peritoneal lavage performed before LPS administration reduced serum cytokine levels by approximately 50% and mortality from 50 to 100%. The effect of peritoneal lavage is due to the removal of peritoneal cells as reinjection of peritoneal cells eliminated the protective effect of lavage on LPS-induced mortality. A special role of peritoneal macrophages in the systemic response to LPS was suggested by the finding that LPS-induced an increase in intracellular TNF-alpha and IL-6 peritoneal macrophages but in neither splenic nor bone marrow macrophages. Intraperitoneal injection of thioglycollate broth 4 days prior to lavage increased the number of peritoneal cells removed by lavage and increased protection from LPS mortality. Peritoneal lavage performed 30 to 120 minutes after the LPS administration completely protected all mice from LPS-induced mortality, suggesting the possibility that such treatment may offer a novel therapeutic approach to septic shock.

Animals↗
PubMed1997

Inflammatory bowel disease: potential therapeutic strategies.

This review deals with potential and possibly primary therapeutics that, through insight into the inflammatory cascade, result in more rational treatment principles replacing the classical therapy of inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). These new therapies might be useful for IBD patients, especially since the 'classical therapy' with agents like glucocorticoids, sulfasalazine, mesalazine, azathioprine, 6-mercaptopurine, cyclosporin and methotrexate is often only moderately effective and may have important side-effects. Controlled trials of the novel agents mentioned in this review have not yet been performed, however.

Animals↗
PubMed1996

Involvement of interleukin-4 and -10 in inflammatory bowel disease.

The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) may be associated with a decreased production of cytokines suppressing macrophage and T-cell functions: interleukins (IL) -4 and IL-10. Serum concentrations of IL-4 and IL-10 were measured using an ELISA technique, and intestinal IL-4 and IL-10 mRNA was detected by a reverse transcriptase polymerase chain reaction (RT-PCR) in 34 patients with inflammatory bowel disease (IBD) (20 with UC and 14 with CD) and compared to 12 control subjects. The superoxide production was measured spectrophotometrically in activated PMNs initially incubated in the presence of IL-4 or IL-10. No differences were found in numbers of cells that might be potential IL-4 or IL-10 producers (T cells, macrophages, B cells, and mast cells) in biopsy specimens using immuno- and histochemistry. IL-4 mRNA was detectable in specimens from 77.8% of the UC patients (P > 0.05) and 0% of the CD patients (P < 0.05), as compared to 81.8 in controls, and was significantly different (P < 0.0001) between UC and CD patients. The IL-10 amplification product was detectable in specimens from 30.0% UC patients (P < 0.003), but not in CD patients (78.6%, P > 0.05) as compared to controls (91.7%). The circulating protein levels of IL-4 were below the detection limit in all groups (detection limit 4 pg/ml), while the median IL-10 concentration was 12.5 pg/ml in UC, 18.1 pg/ml in CD, and 19.5 pg/ml among controls (detection limit 3 pg/ml), which did not differ in any of the three groups (P > 0.05). Finally, the superoxide production was inhibited and delayed by the addition of IL-10 (P < 0.01), whereas IL-4 only delayed this parameter. In conclusion, apart from the well-known suppressive effect on proinflammatory cytokine production, IL-4 delays and IL-10 inhibits superoxide generation. IL-4 mRNA expression is decreased in intestinal tissue from CD patients, while IL-10 mRNA expression is decreased in majority of UC patients, suggesting different immunopathogenesis of the two diseases.

Adult↗
PubMed1996

LFA-1 subunit expression in ulcerative colitis patients.

The adhesion molecule, lymphocyte function associated antigen (LFA-1) consisting of two subunits, CD11a and CD18, mediates lymphocyte migration into tissue and cell effector functions. Previous observations showed no differences in LFA-1 expression by circulating lymphocytes between inflammatory bowel disease patients and controls. The aim of the present work was to study subsets of circulating LFA-1+ lymphocytes in ulcerative colitis (UC) patients versus healthy controls. Peripheral blood mononuclear cells were obtained from 16 UC patients and 10 healthy volunteers. The percentages of CD11alo, CD11ahi, CD18lo, CD18hi T and B cells, as well as Cd25 expression on these cells were studied using double staining with monoclonal antibodies and panning procedures. The percentage of CD11hi and CD18hi T cells was significantly decreased in quiescent UC patients as compared to active disease patients and healthy controls (P < 0.05). The majority of CD25+ T cells were expressing CD11a and CD18 with low density. A detectable percentage, 2% (range 1-6%), of CD11ahiCD25+ (but not CD18hiCD25+) was found in UC patients with moderate to severe disease, but not in those with inactive UC to healthy controls. In conclusion, the percentage of CD11ahi+ and CD18hi+ T cells is decreased in peripheral blood of quiescent UC patients, which is probably associated with the effect of specific treatment. The percentage of CD11ahi+IL-2R alpha+ T cells is increased in peripheral blood of patients with active (moderate and severe) UC, which most likely reflects a sustained T-cell activation due to a persistent inflammatory process.

Adult↗
PubMed1996

Treatment of old mice with IL-2 corrects dysregulated IL-2 and IL-4 production.

Splenic T cells from old BALB/c mice, activated in vitro with antibody to CD3epsilon, secrete more IL-4 but less IL-2 than splenic T cells from young mice. The age-associated increase in IL-4 secretion is associated with a significantly increased concentration of intracellular IL-4 and its mRNA, although there is no increase in the number of activated T cells with intracellular IL-4. In contrast, the age-associated decrease in IL-2 secretion is associated with a significant decrease in the number of activated T cells with intracellular IL-2. In vivo there is a similar age-associated change in the number of activated T cells with detectable cytokine. The number of activated T cells with intracellular IL-4 is comparable in old and young mice, while the number of activated T cells with intracellular IL-2 is significantly decreased in old compared with young mice. Of great interest is the fact that old mice continuously exposed to IL-2 in vivo following the transplantation of J558 cells expressing the transfected IL-2 gene product have an increased number of splenic T cells with intracellular IL-2 that equals the level of such cells observed in young mice. Most important, the effect of continuous IL-2 administration in vivo was stable as spleen cells from old, IL-2-treated mice when stimulated in vitro with anti-CD3epsilon had a young-like pattern of both intracellular IL-2 and IL-4 expression as well as IL-2 and IL-4 secretion following in vitro activation. Thus, it appears that exposure of old mice to exogenous IL-2 can redress the age-associated imbalance in cytokine expression in vivo and cytokine secretion in vitro.

Age Factors↗
PubMed1996

Increased numbers of interleukin-15-expressing cells in active ulcerative colitis.

OBJECTIVES: Interleukin-15 (IL-15) is a novel cytokine sharing many of the activities of IL-2. The goal of this study was to evaluate intracellular and serum IL-15 in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Intracellular expression of IL-15 in peripheral blood mononuclear cells (PBMC) from UC patients, CD patients, and controls was studied using cell permeabilization and staining with monoclonal antibodies. Serum levels of IL-15 were detected using ELISA. RESULTS: Percentage of IL-15 expressing PBMC was increased in UC patients and in five of six of CD patients with moderate and severe disease activity compared with controls. The number of IL-15 expressing cells in patients with active inflammatory bowel disease (IBD) declined within 2 wk of treatment. Serum IL-15 reached detectable levels in 62.5% of UC patients with moderate and severe disease activity but not in UC patients with slight disease activity or in remission, neither in CD patients nor in controls. In vitro lipopolysaccharide (LPS)-induced activation of PBMC from controls was associated with up-regulation of intracellular IL-15 expression (p < 0.01) and release of IL-15. CONCLUSIONS: UC patients with moderate and severe disease activity have increased percentage of IL-15 expressing PBMC, which might be induced by in vivo cell activation and can lead to elevation of released IL-15 in serum. Increased IL-15 expression after in vitro LPS stimulation of control PBMC suggests a nonspecific production of this cytokine during the immunoinflammatory response.

Adult↗
PubMed1995

Interleukin-2 receptor alpha and beta chain expression by circulating alpha beta and gamma delta T cells in inflammatory bowel disease.

The pathogenetic role of activated alpha beta and gamma delta T cells in inflammatory bowel disease (IBD) is not well defined. To elucidate this, interleukin-2 receptor (IL-2R) alpha and IL-2R beta single chain expression and coexpression by peripheral blood TCR alpha beta + cells and TCR gamma delta + cells was studied in 21 patients with ulcerative colitis (UC), 25 with Crohn's disease (CD), and 15 controls. The percentages of IL-2R alpha + beta-, IL-2R alpha-beta +, and IL-2R alpha + beta + TCR alpha beta + cells were increased in IBD patients with moderate and severe disease activity, as compared to controls (P < 0.01). In contrast, the percentages of IL-2R alpha-beta + and IL-2R alpha + beta + TCR gamma delta + cells were increased in patients with inactive UC (P < 0.01), but not in CD. The results suggest that activated alpha beta T cells are involved in the development of IBD. The differences in gamma delta T cell IL-2R expression between inactive UC and CD may correspond to a yet undefined etiopathogenetic difference between these two diseases.

Adolescent↗
PubMed1995

Circulating soluble interleukin-2 receptor alpha and beta chain in inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease is characterized by T cell activation. Activated T cells shed interleukin-2 receptors (IL-2R) in a soluble form. A positive correlation between sIL-2R alpha (CD25) and disease activity in inflammatory bowel disease has been shown previously, whereas IL-2R beta (CD122) has never before been investigated in this respect. Serum from 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy volunteers was obtained. METHODS: Disease activity was scored according to a semiquantitative score for UC and by Crohn's disease activity index for CD. sIL-2R alpha and -beta chains were assessed by a sandwich ELISA technique using monoclonal antibodies specific for CD25 and CD122, respectively. RESULTS: The median concentration of sIL-2R alpha was 4424 pg/ml in healthy controls, 6460 in UC (p < 0.004), and 6371 in CD (p < 0.01). The corresponding value of sIL-2R beta in healthy volunteers was 605 pg/ml; in active UC, significantly lower levels were found at 233 pg/ml (p < 0.01), whereas in inactive UC, no such difference was observed at 725 pg/ml (p > 0.05). In CD, the levels were 839 pg/ml in inactive and 920 pg/ml in active disease stages (p > 0.05 vs controls). A positive and significant correlation existed between sIL-2R levels of alpha and beta chains in CD (r = 0.64; p < 0.01) but not in UC (r = -0.32; p > 0.05) or in healthy volunteers (r = 0.16; p > 0.05). CONCLUSION: Future longitudinal studies will be necessary to learn whether this newly assessed sIL-2R beta (CD122), which may interfere with IL-15R, could be used to predict disease exacerbation and to monitor anti-inflammatory therapy in UC.

Adult↗