Biomedical subjects

V Barak

Publications and source records attributed to V Barak.

At least 37 records · Page 2Linked to original sources

PubMed1999

Anti-idiotype immunomodulation of experimental anti-phospholipid syndrome via effect on Th1/Th2 expression.

Mice with experimental anti-phospholipid syndrome (APS), induced by active immunization with a human anti-cardiolipin MoAb (H-3), were treated with mouse anti-idiotypic MoAb (anti-H3, named S2.9) and with an irrelevant anti-idiotype. The immunized mice produced high titres of mouse anti-cardiolipin antibodies along with clinical manifestations of experimental APS: prolonged activated partial thromboplastin time (aPTT), thrombocytopenia and high rate of fetal loss. Treatment with the specific anti-Id (S2.9) as a whole molecule or F(ab)2 fraction, resulted in a decrease in serum levels of the anti-cardiolipin antibodies, rise in platelet count, shortened aPTT and reduced rate of fetal loss. The anti-Id effect was associated with a rise in the number of IL-2 and interferon-gamma (IFN-gamma)-secreting cells (Th1) and reduction in IL-4- and IL-6-secreting cells (Th2). The beneficial effect of the anti-Id treatment in mice with experimental APS induced by active immunization with an idiotype further supports the idiotypic aetiology of experimental APS and points to the role of Th1 cytokines in suppression of its manifestations.

Abortion, Habitual↗

PubMed1999

The tumor necrosis factor family and and correlation with disease activity and response to treatment in hairy cell leukemia.

Hairy cell leukemia (HCL) is a well recognized indolent B-cell lymphoproliferative disorder. HCL cell proliferation is regulated by growth factors and cytokines, of which tumor necrosis factor-alpha (TNF-alpha) may be one of the most important. The mechanism of TNF-alpha-induced HCL cell growth is mediated via 2 receptors, which are present in both cellular and soluble forms. In this study we determined the serum levels of TNF-alpha and their soluble receptors - sTNF-R60 and sTNF-R80 - in 23 HCL patients and correlated them with clinical parameters before and after therapy. Patients were classified according to their clinical status as either "active" at diagnosis or during relapse and "non-active" (responding to therapy with partial and complete remission). Most patients were treated with 2-CDA, following which serum levels of TNF-alpha, sTNF-R60 and sTNF-R80 were significantly decreased, particularly in CR. Significant differences in paired observation values were noted for TNF-alpha and sTNF-R80, indicating a good correlation with the clinical status of disease, but this was not the case for sTNF-R60 (coefficients of correlation between levels of TNF-alpha and sTNF-R80 and of TNF-alpha and sTNF-R60 were r = 0.85 and r= 0.64, respectively). These results suggest that decreases in both TNF-alpha and sTNF-R80 are indicative of response to treatment, while increased levels accompany active disease. Accordingly, we conclude that serum levels of the TNF family, as for the sIL-2R and IL-1 family, may also be used as sensitive markers for monitoring HCL status. Levels may be indicative of the clinical efficacy of therapy and can be used as an indicator of the presence of residual disease.

2-Chloroadenosine↗

PubMed1999

Activation of murine macrophages by lipoprotein and lipooligosaccharide of Treponema denticola.

We have recently demonstrated that the periodontopathogenic oral spirochete Treponema denticola possesses membrane-associated lipoproteins in addition to lipooligosaccharide (LOS). The aim of the present study was to test the potential of these oral spirochetal components to induce the production of inflammatory mediators by human macrophages, which in turn may stimulate tissue breakdown as observed in periodontal diseases. An enriched lipoprotein fraction (dLPP) from T. denticola ATCC 35404 obtained upon extraction of the treponemes with Triton X-114 was found to stimulate the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 (IL-1) by mouse macrophages in a dose-dependent manner. Induction of NO by dLPP was at 25% of the levels obtained by Salmonella typhosa lipopolysaccharide (LPS) at similar concentrations, while IL-1 was produced at similar levels by both inducers. dLPP-mediated macrophage activation was unaffected by amounts of polymyxin B that neutralized the induction produced by S. typhosa LPS. dLPP also induced NO and TNF-alpha secretion from macrophages isolated from endotoxin-unresponsive C3H/HeJ mice to an extent similar to the stimulation produced in endotoxin-responsive mice. Purified T. denticola LOS also produced a concentration-dependent activation of NO and TNF-alpha in LPS-responsive and -nonresponsive mouse macrophages. However, macrophage activation by LOS was inhibited by polymyxin B. These results suggest that T. denticola lipoproteins and LOS may play a role in the inflammatory processes that characterize periodontal diseases.

Animals↗

PubMed1999

Cerebrospinal cytokine levels in patients with acute depression.

There is increasing evidence for an association between the alteration of cytokine concentrations in blood and the pathophysiology of depressive disorders. Studies in humans have not investigated CSF cytokine concentrations and their relationship to depressive disorders. This study reports on the association of the CSF concentration of proinflammatory cytokines, IL-1beta, IL-6 and TNFalpha, and major depressive disorders. CSF samples were obtained from 13 hospitalized patients with acute unmedicated severe depression and were compared with 10 control subjects. Compared to the control group, the depressed patient group had higher CSF concentrations of IL-1beta, lower IL-6 and no change in TNFalpha. A positive correlation was found between serum IL-1beta and the severity of depression. These results indicate a unique profile for CSF proinflammatory cytokines in acute depression. These findings merit further investigation and if replicated may possibly offer immunological treatment options for depression.

Acute Disease↗

PubMed1999

Cytokines in Gaucher's disease.

Gaucher's disease (GD) is characterized by hepatosplenomegaly, bone marrow infiltration, osteonecrosis, which may all be associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. Levels of serum cytokines, which are soluble products of mononuclear phagocytes (MNP), were evaluated in 24 GD patients. Levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble interleukin-2 receptor (sIL-2R) in GD patients were significantly higher than in normal controls. We attempted to correlate cytokine levels with disease severity. Type I GD patients with more severe clinical manifestations had significantly higher levels of IL-1beta, IL-1Ra and IL-6, relative to type I patients with milder disease. Three patients homozygous for the 1448C mutation with neuropathic type III disease, had significantly higher levels of sIL-2R than type I patients or controls. We speculate that cytokine over-expression may relate to the pathophysiology of some of the clinical manifestations of GD. Thus, the elevated IL-1beta, TNF-alpha and IL-6 levels may induce the bone manifestations, the neutrophil chemotaxis and the increased incidence of hyper-gammaglobulinemia present in GD patients.

Chemotaxis, Leukocyte↗

PubMed1999

Follicular fluid levels of vascular endothelial growth factor. Are they predictive markers for ovarian hyperstimulation syndrome?

OBJECTIVE: To determine the possible predictive role of vascular endothelial growth factor (VEGF) levels in the follicular fluid (FF) at the time of oocyte retrieval in the development of ovarian hyperstimulation syndrome (OHSS) and its possible origin. STUDY DESIGN: FF was obtained from 174 high-responder patients at the time of oocyte retrieval. The study group comprised 16 high-responder patients who developed early, severe OHSS and from whom serum and peritoneal fluid (PF) were obtained during the active phase of the syndrome. These women were compared to 16 high-responder patients who did not develop OHSS. An additional control group comprised 16 low-responder patients who also did not develop OHSS. The FF, serum and PF samples were tested for VEGF by enzymelined immunosorbent assay. RESULTS: No differences in the FF VEGF levels were found among the OHSS group (1,742.3 +/- 522.4 pg/mL), the high-responder group that did not develop OHSS (1,802.0 +/- 584.3 pg/mL) and the low-responder group (1,686.7 +/- 374.2 pg/mL). In the OHSS group, no differences were found between the serum and PF VEGF levels (247.3 +/- 31.4 and 642.9 +/- 328.3 pg/mL, respectively). No correlation was found between the FF concentrations of VEGF and the mean serum 17-beta estradiol levels or number of oocytes retrieved. CONCLUSION: We conclude that preovulatory FF levels should not serve as a possible predictive factor for development of OHSS. The increased capillary permeability found in OHSS may be due to its systemic effect.

Case-Control Studies↗

PubMed1998

Oral tolerance to low dose beta 2-glycoprotein I: immunomodulation of experimental antiphospholipid syndrome.

Oral tolerance was induced in BALB/c mice by feeding low dose beta2-glycoprotein I (beta2GPI). The beta2GPI-fed mice did not develop serologic and clinical markers of experimental antiphospholipid syndrome (APS) upon immunization with the autoantigen. The treated group was characterized by low titers of serum anti-beta2GPI and anticardiolipin Abs in the serum, lack of fetal resorptions, low incidence of thrombocytopenia, and normal aPTT (activated partial thromboplastin time) values. Beta2GPI given orally before priming with beta2GPI resulted in complete prevention of experimental APS development; beta2GPI given at an early stage of the disease reduced clinical manifestations. However, administration of beta2GPI 70 days postimmunization had a less significant effect on disease expression. Tolerized mice exhibited a diminished T lymphocyte proliferation response to beta2GPI in comparison with beta2GPI-immunized mice fed with OVA. When nontolerant beta2GPI-primed T lymphocytes were mixed with T lymphocytes derived from tolerized mice, a significant inhibition of proliferation upon exposure to beta2GPI was observed. The induction of suppression was beta2GPI specific and driven, as well as TGF-beta mediated. The beta2GPI-specific response of T lymphocytes from the beta2GPI-fed mice was reversed by anti-TGF-beta Abs. The tolerance was adoptively transferred by CD8+ T cells from the tolerized mice into naive mice. Those CD8+ cells were MHC class I restricted, found to secrete TGF-beta, and had no cytolytic activity. Oral administration of beta2GPI suppressed priming of CTLs in the recipient mice. In sum, beta2GPI-induced oral tolerance has an immunomodulatory effect in experimental APS, demonstrating the importance of beta2GPI in the pathogenesis of the disease.

Administration, Oral↗

PubMed1998

Cytokine production in human mixed leukocyte reactions performed in serum-free media.

The mixed leukocyte reaction (MLR) is an in vitro test commonly performed in a serum-containing medium (SCM), and used to study allorecognition and cellular immunity accompanied by cytokine release. We investigated the possibility of performing the MLR test in serum-free media (SFM) by comparing human leukocyte proliferation and cytokine release in MLRs performed in SFM and SCM. Of the four SFM tested, only Biotarget- was as effective as SCM in supporting leukocyte proliferation and IL-2 secretion. Both phenomena were observed only in allogeneic combinations. The levels of IL-1, IL-6, and TNFalpha in allogeneic MLR combinations in SFM were half those in SCM cultures; the kinetics of their release were the same. With the exception of IL-2, a high degree of spontaneous release of the other three cytokines analyzed was observed in responder cells, in irradiated stimulator cells, and in autologous combinations cultured in both SCM and SFM. It appears that unlike IL-2, the cytokines IL-1, IL-6, and TNFalpha are nonspecifically produced in MLR and cannot serve as sensitive indices of HLA disparity.

Culture Media, Serum-Free↗

PubMed1998

Evaluation of tissue polypeptide specific antigen, CYFRA 21-1, and carcinoembryonic antigen in nonsmall cell lung carcinoma: does the combined use of cytokeratin markers give any additional information?

BACKGROUND: Recently developed tissue polypeptide specific antigen (TPS) and CYFRA 21-1 assays determine the soluble cytokeratin 18 and 19 fragments, respectively, in serum. The authors compared the value of TPS, CYFRA 21-1, and carcinoembryonic antigen (CEA) for the diagnosis, staging, prognosis, and monitoring of patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The study included 85 patients with benign lung diseases and 94 patients with NSCLC. TPS, CYFRA 21-1, and CEA serum levels were measured with commercial kits. RESULTS: The following were demonstrated: 1) CYFRA 21-1 and TPS levels, but not CEA levels, differed significantly between NSCLC patients with operable disease (Stages I-IIIA) and those with inoperable disease (Stages IIIB-IV). 2) The correlation coefficient between CYFRA 21-1 and TPS increased with the progression of NSCLC from Stages I-IIIA (r = 0.41, P = 0.04) to Stages IIIB-IV (r = 0.70, P < 0.001). 3) Multivariate analysis identified TPS and CYFRA 21-1 as significant predictors of survival, with relative risks of 2.57 (P = 0.001) and 2.05 (P = 0.01), respectively. For cases in which both cytokeratin markers were positive, the relative risk was 6.4 (P < 0.0001) compared with cases in which both were negative. 4) For the group with inoperable disease, the combined use of TPS and CYFRA 21-1 allowed for the definition of 3 sets of patients with significantly different median survival times (14.3 months vs. 7.4 months vs. 2.6 months). 5) The percentages of marker evaluations concordant with results of clinical assessments of response to therapy were 75.0%, 72.2%, and 61.1% for CYFRA 21-1, TPS, and CEA, respectively. CONCLUSIONS: These findings suggest that, for NSCLC patients, CYFRA 21-1 and TPS are significant prognostic factors and effective monitors of therapy. The combined use of these cytokeratin markers may provide additional information for prognosis.

Adult↗

PubMed1998

Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin-3 and granulocyte-macrophage colony-stimulating factor expression.

OBJECTIVE: To evaluate the immunomodulatory potential of ciprofloxacin in mice with experimental antiphospholipid syndrome (APS). METHODS: Ciprofloxacin or ceftazidime (control antibiotic) was given to mice with experimentally induced APS. The titers of autoantibodies, levels of cytokines, and number of cytokine-producing cells were determined by enzyme-linked immunosorbent assay. Myeloid progenitor cells were determined by granulocyte-macrophage colony-forming unit, and interleukin-3 (IL-3) messenger RNA (mRNA) was tested by Northern analysis. RESULTS: A decrease in the incidence of pregnancy loss and an improvement in the clinical manifestations of APS were noted in the mice treated with ciprofloxacin, compared with the mice given ceftazidime. The effect of ciprofloxacin was found to be associated with increased serum levels of IL-3 and with increased IL-3 mRNA transcription in the splenocytes. Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was documented by elevated titers in the sera and elevated numbers of colony-forming cells in the bone marrow. CONCLUSION: Ciprofloxacin prevents the manifestations of experimental APS. This effect may be associated with increased IL-3 levels and GM-CSF expression.

Adjuvants, Immunologic↗

PubMed1998

Changes in cytokine production of breast cancer patients treated with interferons.

A clinical randomized study was performed on advanced breast cancer patients who were treated by interferons (IFN) beta and gamma in combination with hormonotherapy (Megace or Tamoxifen). Cytokine levels (IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma) and sIL-2R of individual patients before, during (3 months) and after (6 months) therapy were evaluated and correlated to clinical response according to UICC criteria (responder patients-partial or Complete Response versus non-responder patients-Stable/Progression). Decreases in IL-1beta, IL-6 and sIL-2R were associated with clinical response to therapy versus increases in their levels which corresponded to progression of disease. A significant and dramatic increase in IFN-gamma levels was associated with a favourable response to therapy in the IFNs-treated patients, mainly in the group of Tamoxifen. Baseline levels of sIL-2R and of IFN-gamma were prognostic of clinical response and were found to be the most sensitive cytokine parameters for defining the clinical utility of the combination of IFNs and hormonotherapy in breast cancer patients.

Antineoplastic Agents, Hormonal↗

PubMed1998

Prevalence of hypophosphatemia in sepsis and infection: the role of cytokines.

BACKGROUND: Sepsis occurs following the presence of bacteria in the circulation and is associated with fever, hyperthermia, and hypotension. Hypophosphatemia develops in the early stages of sepsis. High levels of inflammatory cytokines also characterize early sepsis. AIM: The aim of the present study was to correlate hypophosphatemia with cytokines and cytokine receptor levels during early sepsis. We aimed to reestablish the results obtained from patients in an in vivo experimental model, in order to understand the mechanism of hypophosphatemia induction in early sepsis. METHODS: Ninety-nine patients were enrolled in this study and their clinical condition was classified as the presence of infection, sepsis, and bacterial growth in blood cultures. Phosphate levels and cytokine levels were recorded. In order to determine whether hypophosphatemia is correlated to the increased inflammatory cytokines, we injected normal mice with recombinant cytokines and studied their effect on phosphate levels. RESULTS: Our results revealed that 80% of the septic patients had hypophosphatemia associated with very high levels of tumor necrosis factor (TNF)alpha and interleukin (IL)-6 and of soluble IL receptor (sIL)-2R and IL-6R, especially in those patients with positive blood cultures. Injection of IL-6, TNFalpha and IL-1beta in mice markedly decreased the phosphate serum levels. CONCLUSIONS: Significant associations were demonstrated between high levels of inflammatory cytokines and their receptors and between serum phosphate levels, especially in patients with positive blood culture. Our results point to a correlation between the high inflammatory cytokines levels and hypophosphatemia during early sepsis. Cytokine levels and hypophosphatemia may be included in sepsis evaluation and prognosis. Anticytokine strategies might, therefore, reverse hypophosphatemia and other parameters of sepsis.

Cytokines↗

PubMed1998

Cytokeratin markers in malignant pleural mesothelioma.

Previously available serum tumor markers had a low clinical value in malignant pleural mesothelioma (MPM). The recently developed tissue polypeptide-specific antigen (TPS) and CYFRA 21-1 assays identify the soluble cytokeratin 18 and 19 fragments, respectively. In MPM these cytokeratins are expressed and may therefore be used as serum tumor markers. In this preliminary study, TPS and CYFRA 21-1 assays were evaluated to determine their potential for management of patients with MPM. Carcinoembryonic antigen (CEA) was evaluated as an additional marker. The study group consisted of 95 patients with benign lung and pleural diseases (BLPD), 14 patients with MPM, 41 patients with adenocarcinoma of lung (AC), and 40 patients with squamous cell carcinoma of lung (SQC). The utilized cutoff points corresponded to a 95% specificity for patients with BLPD. In MPM, TPS showed greater sensitivity (64.3%) than CYFRA 21-1 (50.0%), while CEA showed no sensitivity. In SQC, the marker CYFRA 21-1 had the highest sensitivity (52.5%), whereas in AC the most sensitive marker was CEA (56.1%). Significantly lower levels of CEA were found in MPM compared with BLPD (p < 0.001) or AC and SQC (p < 0.0001). Conversely, TPS levels in MPM were significantly higher than in SQC (p < 0.05). Close correlation of various individual pretreatment marker levels was observed only between TPS and CYFRA 21-1, both in MPM (r = 0.84; p < 0.001) and in non-small cell lung cancer (NSCLC) (r = 0.71; p < 0.001). In serial determinations of the markers during chemotherapy of MPM (n = 10), TPS and CYFRA 21-1 were shown to demonstrate more or less the same pattern of reactivity, although the changes in the TPS levels better reflected the clinical response to therapy. In conclusion, TPS seems to be a more sensitive marker than CYFRA 21-1.

Antigens, Neoplasm↗

PubMed1998

Cytokine evaluation in throat infections.

Inflammatory cytokines have been shown to play an important role in the pathogenesis of various inflammatory processes. In throat infections, intracellular inflammatory cytokines have been detected from the sites of inflammation. The present study aimed to evaluate serum cytokine levels of patients with throat infections and correlate them to the inflammatory parameters and type of inflammation. Significantly higher inflammatory cytokine levels (interleukin [IL]-6 > 7 pg/mL, IL-1 > 1 beta pg/mL, tumor necrosis factor alpha > 1 pg/mL) were detected in most of the patients as opposed to healthy controls. Clinical parameters of infection (fever > 38 degrees C, leukocytosis > 11,000 white blood cells per cubic millimeter, polymorphonuclear neutrophils > 75%) were significantly correlated with high levels of inflammatory cytokines: mainly IL-6 and tumor necrosis factor alpha, and to a lesser degree with IL-1 beta. No correlation, however, was found between the type of inflammation and cytokine levels. The present study indicates a role of inflammatory cytokines in the pathogenesis of throat infections and the need for an anti-inflammatory and anticytokine therapeutic approach.

Adolescent↗

PubMed1998

Effects of tetracyclines on the pathologic activity of endotoxin: in vitro and in vivo studies.

Lipopolysaccharide (LPS) is considered to be one of the major virulence factors of Gram-negative bacteria. Recently, tetracyclines (TTCs) were found to prevent the patho-physiological changes associated with LPS in vivo and the secretion of inflammatory mediators in vitro. However, the mechanism by which TTCs prevents LPS-induced pathology in vivo is still unclear. In order to shed light on that problem, we carried out in vitro and in vivo experiments. TTC inhibited the secretion of nitric oxide (NO) and TNF alpha from LPS-stimulated macrophages and inhibited macrophage-induced thymocyte proliferation. However, TTC inhibited NO secretion with use of concentrations five-fold lower than those that inhibited TNF alpha secretion and thymocyte proliferation. The secretion of NO was inhibited by the addition of TTC to the cultures up to 6 hrs post-LPS stimulation. TTC inhibition of LPS-induced NO secretion was not reversed by the addition of recombinant TNF alpha, and TTC inhibition of LPS-induced TNF alpha secretion was not reversed by the addition of NO donor. These results suggest that the inhibition of TNF alpha by TTC is not the result of the inhibition of LPS-induced NO secretion or vice versa. In vivo experiments had shown that TTC prevented mortality in LPS-treated mice, but not in mice pre-sensitized with galactosamine prior to the LPS challenge. These results suggest that TTC activity in vivo is due not to the suppression of synthesis of inflammatory mediators but rather to the induction of acute phase-like response, which antagonizes the LPS-induced activity.

Acute-Phase Reaction↗

PubMed1998

Immunomodulation of murine experimental SLE-like disease by interferon-gamma.

The objective of this study was to assess the impact of murine recombinant IFN-gamma and anti-IFN-gamma monoclonal antibody on the BALB/c mice experimental model of lupus. BALB/c female mice were immunized with a human anti-DNA antibody that carries the 16/6 idiotype. These mice were divided into several therapeutic groups according to different treatment strategies; injection with mouse recombinant IFN-gamma, anti-IFN-gamma mAb, phosphate-buffered saline (PBS), irrelevant mouse IgG and control groups that were neither treated nor immunized with the human anti-DNA antibody. The administration of IFN-gamma, intensified the degree of clinical, histological and serological parameters in this model of BALB/c murine lupus. This immunomanipulation decreased the mice longevity. All the laboratory parameters reflected acceleration of the disease in the IFN-gamma treated group as an elevated sedimentation rate, decreased white blood cell count and the development of massive proteinuria. One month after the boost injection, all the mice that were immunized with the anti-DNA antibody, developed high titers of autoantibodies; however, following an additional month, their levels declined in the IFN-gamma treated group. These findings were in concordance with an increased glomerular deposition of immune complexes in the IFN-gamma treated mice. IFN-gamma upregulated the levels of IL-4 and increased the number of IL-4 and IL-6 secreting splenocytes. In conclusion IFN-gamma administration can aggravate the clinical and laboratory outcome of 16/6 id induced lupus in BALB/c mice.

Animals↗

PubMed1998

Correlation of serum levels of interleukin-1 family members with disease activity and response to treatment in hairy cell leukemia.

Hairy cell leukemia (HCL) is a well-recognized chronic lymphoproliferative disorder of B cell lineage, which may be regulated by growth factors including cytokines and cytokine antagonists. Previous studies have shown a good correlation between circulating soluble interleukin-2 receptor (sIL-2R) levels and disease activity and response to therapy was always associated with a decrease in sIL-2R levels. The interleukin-1 (IL-1) family of agonists and antagonists may also be involved in the regulation of hematopoietic malignancies. In the present study, we evaluated members of the IL-1 family (IL-1beta, IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble receptors Type I and Type II (IL-1sRI and IL-1sRII) in 23 patients with HCL. Patients were classified according to the clinical state of their disease. Most were treated with 2-chloro-2'-deoxyadercosine (2-CDA) and treatment was associated with a significant decrease in the serum levels of sIL-2R, IL-1beta and IL-1sRII in patients achieving a complete or partial response. In contrast to the above, levels of IL-1Ra increased during response to treatment and clinical response to 2-CDA was associated with an increase of 122% in IL-1Ra levels, in parallel with a decrease of 63% in IL-1beta and 47% in IL-1sRII levels. These results suggest that the balance between IL-1beta, IL-2 and their soluble receptors or antagonists may be involved in the pathogenesis and immunoregulation of HCL. Serum levels of these cytokines may therefore be used to monitor therapeutic efficacy of therapy in HCL and to detect any residual disease.

2-Chloroadenosine↗

PubMed1998

Dysregulation of inflammatory cytokines in unrelated bone marrow transplantation.

The dysregulation of cytokines is thought to play a role in the inflammatory and allospecific components of graft-versus-host disease (GVHD) and graft rejection (GR) post allogeneic bone marrow transplantation (BMT). Both complications occur post unrelated BMT at significantly higher frequencies than post BMT from identical sibling donors. The levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta, IL-6, IL-10 and IL-12 following unrelated BMT were measured to examine cytokine dysregulation involvement in GVHD and GR. Of the 26 patients included in this study, 15 developed GVHD (14 acute; 1 acute and chronic), 5 had GR and 6 had uneventful BMT. TNF-alpha was markedly elevated in 13/15 of the patients with GVHD and in 3/5 patients with GR. IL-6 was elevated in patients with acute GVHD and with GR. IL-12 levels were similar in pre- and post-BMT sera. No correlation was found between HLA-C match and cytokine levels. In conclusion, a positive correlation was found between elevated levels of TNF-alpha, IL-6 and IL-10, and GVHD (p < 0.05, p < 0.005 and p < 0.002 respectively) and GR (p < 0.01).

Adolescent↗