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Cytotoxic Factors (cytotoxic + factor)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Cytotoxic factor-autoantibodies: possible role in the pathogenesis of dengue haemorrhagic fever

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2001
U.C. Chaturvedi
Abstract During dengue virus infection a unique cytokine, cytotoxic factor (hCF), is produced that is pathogenesis-related and plays a key role in the development of dengue haemorrhagic fever (DHF). However, what regulates the adverse effects of hCF is not known. We have previously shown that anti-hCF antibodies raised in mice, neutralise the pathogenic effects of hCF. In this study we have investigated the presence and levels of hCF-autoantibodies in sera of patients with various severity of dengue illness (n=136) and normal healthy controls (n=50). The highest levels of hCF-autoantibodies (mean±S.D.=36±20 U ml,1) were seen in patients with mild illness, the dengue fever (DF), and 48 out of 50 (96%) of the sera were positive. On the other hand the hCF-autoantibody levels declined sharply with the development of DHF and the levels were lowest in patients with DHF grade IV (mean±S.D.=5±2 U ml,1; P=<0.001 as compared to DF). Only one of the 13 DHF grade IV patients had an antibody level above the ,cut-off' value (mean plus 3 S.D. of the control sera). The analysis of data with respect to different days of illness further showed that the highest levels of hCF-autoantibodies were present in DF patients at >9 days of illness. Moreover, the DF patients at all time points, i.e. 1,4, 5,8 and >9 days of illness had significantly higher levels of hCF-autoantibodies (P<0.001) than patients with DHF grade I, II, III and IV. In addition DHF grade I and grade II patients had significantly more positive specimens than DHF grade III and grade IV patients at all time points. These results suggest that elevated levels of hCF-autoantibodies protect the patients against the development of severe forms of DHF and, therefore, it may be useful as a prognostic indicator. [source]

Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2000
U.C. Chaturvedi
Abstract Dengue virus produces a mild acute febrile illness, dengue fever (DF) and a severe illness, dengue hemorrhagic fever (DHF). The characteristic feature of DHF is increased capillary permeability leading to extensive plasma leakage in serous cavities resulting in shock. The pathogenesis of DHF is not fully understood. This paper presents a cascade of cytokines, that in our view, may lead to DHF. The main feature is the early generation of a unique cytokine, human cytotoxic factor (hCF) that initiates a series of events leading to a shift from Th1-type response in mild illness to a Th2-type response resulting in severe DHF. The shift from Th1 to Th2 is regulated by the relative levels of interferon-gamma and interleukin (IL)-10 and between IL-12 and transforming growth factor-,, which showed an inverse relationship in patients with DF. [source]

Altered conjugate formation and altered apoptosis of multidrug-resistant human leukemia cell line affects susceptibility to killing by activated natural killer (NK) cells

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004
Robin S. Treichel
Abstract Most leukemias that exhibit P-glycoprotein (P-gp)-associated multidrug resistance (MDR) exhibit reduced susceptibility to immune cytotoxicity mediated by natural killer (NK) cells. To explore this phenomenon we investigated N6/ADR, a doxorubicin-selected, P-gp-positive variant of the human acute lymphoblastic leukemia (ALL) cell line NALM6. Each stage of the NK cytolytic pathway, (binding, activation and killing) was evaluated to identify the alterations responsible for the reduced cytotoxicity of the variant relative to its drug-sensitive parental line. The major cause of the decreased susceptibility to NK cytolysis was found to be reduced conjugate formation by the MDR variant. Activation of NK effectors by parental and MDR cells with concomitant release of tumor necrosis factor-alpha (TNF-,) correlated with conjugate formation. N6/ADR was also more resistant than NALM6 to antibody-dependent cellular cytotoxicity and to cytotoxic factors released from NK cells as measured both by 51Cr-release and by DNA fragmentation. This is the first report of a P-gp-positive leukemic line that exhibits reduced conjugate formation as well as increased resistance to NK-mediated killing mechanisms. Our results suggest caution in the use of NK-based immunotherapy as an alternative treatment for multidrug-resistant leukemias. © 2003 Wiley-Liss, Inc. [source]

Attenuation of proliferation in oligodendrocyte precursor cells by activated microglia

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010
Deanna L. Taylor
Abstract Activated microglia can influence the survival of neural cells through the release of cytotoxic factors. Here, we investigated the interaction between Toll-like receptor 4 (TLR4)-activated microglia and oligodendrocytes or their precursor cells (OPC). Primary rat or N9 microglial cells were activated by exposure to TLR4-specifc lipopolysaccharide (LPS), resulting in mitogen-activated protein kinase activation, increased CD68 and inducible nitric oxide synthase expression, and release of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6). Microglial conditioned medium (MGCM) from LPS-activated microglia attenuated primary OPC proliferation without inducing cell death. The microglial-induced inhibition of OPC proliferation was reversed by stimulating group III metabotropic glutamate receptors in microglia with the agonist L-AP4. In contrast to OPC, LPS-activated MGCM enhanced the survival of mature oligodendrocytes. Further investigation suggested that TNF and IL-6 released from TLR4-activated microglia might contribute to the effect of MGCM on OPC proliferation, insofar as TNF depletion of LPS-activated MGCM reduced the inhibition of OPC proliferation, and direct addition of TNF or IL-6 attenuated or increased proliferation, respectively. OPC themselves were also found to express proteins involved in TLR4 signalling, including TLR4, MyD88, and MAL. Although LPS stimulation of OPC did not induce proinflammatory cytokine release or affect their survival, it did trigger JNK phosphorylation, suggesting that TLR4 signalling in these cells is active. These findings suggest that OPC survival may be influenced not only by factors released from endotoxin-activated microglia but also through a direct response to endotoxins. This may have consequences for myelination under conditions in which microglial activation and cerebral infection are both implicated. © 2010 Wiley-Liss, Inc. [source]

Fetal Ethanol Exposure Disrupts the Daily Rhythms of Splenic Granzyme B, IFN- ,, and NK Cell Cytotoxicity in Adulthood

ALCOHOLISM, Issue 6 2006
Alvaro Arjona
Background: Circadian (and daily) rhythms are physiological events that oscillate with a 24-hour period. Circadian disruptions may hamper the immune response against infection and cancer. Several immune mechanisms, such as natural killer (NK) cell function, follow a daily rhythm. Although ethanol is known to be a potent toxin for many systems in the developing fetus, including the immune system, the long-term effects of fetal ethanol exposure on circadian immune function have not been explored. Methods: Daily rhythms of cytotoxic factors (granzyme B and perforin), interferon- , (IFN- ,), and NK cell cytotoxic activity were determined in the spleens of adult male rats obtained from mothers who were fed during pregnancy with chow food or an ethanol-containing liquid diet or pair-fed an isocaloric liquid diet. Results: We found that adult rats exposed to ethanol during their fetal life showed a significant alteration in the physiological rhythms of granzyme B and IFN- , that was associated with decreased NK cell cytotoxic activity. Conclusion: These data suggest that fetal ethanol exposure causes a permanent alteration of specific immune rhythms that may in part underlie the immune impairment observed in children prenatally exposed to alcohol. [source]