Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lymphotoxin-alpha”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

Expression of cell adhesion molecules in posterior uveitis.

Cells in the eye express surface molecules that direct leukocyte migration during ocular inflammation. We studied the expression of intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and endothelial leukocyte adhesion molecule-1 in six enucleated eyes from patients with uveitis and in seven normal control eyes. Lymphocyte function-associated antigen-1 was expressed on infiltrating lymphocytes and intercellular adhesion molecule-1 was expressed on endothelial cells of retinal and choroidal blood vessels and the retinal pigment epithelium in all uveitic eyes, but in none of the normal control eyes. Ocular inflammatory cells stained strongly positive for tumor necrosis factor alpha in all eyes with uveitis, but four of six uveitic eyes showed mild staining for tumor necrosis factor beta and interferon gamma. Cell adhesion molecules are expressed in eyes with posterior uveitis and may be regulated by cytokines such as tumor necrosis factor alpha.

Adult↗
PubMed1992

Inhibitory effects of interleukin 6 on immunity. Possible implications in burn patients.

Certain disease states are associated with abnormal increases in the monokine interleukin 6. Increased levels of interleukin 6 have been demonstrated in serum from patients with burns and are associated with systemic increases in endotoxin levels. Using a murine in vitro experimental model, we have studied the effects of interleukin 6 on various measures of immunity. Our data indicate that levels equivalent to the concentrations found in serum of burn victims inhibit T-cell proliferation. The inhibitory effect is dose and time dependent, is specific for T cells, is not due to impairment of interleukin 2 production or of interleukin 2 receptor expression, and is dependent on macrophages. These data suggest that extraordinary increases in interleukin 6 levels may be related to impaired T-cell responses and to an increased susceptibility to infection in the patient with burns.

Animals↗
PubMed1996

Elevated levels of tumor necrosis factor-beta, gamma-interferon, and IL-6 mRNA in Castleman's disease.

Castleman's disease (CD) is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes. CD may be localized or multifocal, and is often associated with signs and symptoms of generalized inflammation. The systemic manifestations of CD have been previously attributed to an overproduction of interleukin-6 (IL-6) by the tumor, although there is evidence that IL-6 is not responsible for all of the symptoms. We describe a 9-year-old boy who developed Castleman's disease with systemic findings of hypochromic microcytic anemia, growth arrest, inflammation, and hyperimmunoglobulinemia. Following surgical resection, all of the symptoms and laboratory abnormalities resolved. Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis of the tumor, we found elevated levels of IL-6 mRNA as expected, but also elevated levels of tumor necrosis factor beta (TNF-beta) and gamma interferon (gamma-IFN) mRNA. Because these cytokines are mediators of immune regulation and inflammation, we propose that TNF-beta and gamma-IFN also play an important role in the pathophysiology of Castleman's disease.

Castleman Disease↗
PubMedDate not supplied

Lymphocytotoxic antibodies in SLE patients and their relatives.

A search for lymphocytotoxic antibodies in 50 SLE patients and in 109 of their blood relatives revealed an incidence of cold-reacting antibodies of 80% and 39% respectively, as compared with 15% in 110 normal blood donors paired for age, sex, and racial origin. The antibodies were also present in 7 of 18 (39%) of the spouses of SLE patients. Lymphocytotoxic antibodies exhibited broad reactivity in all groups, although positive SLE sera showed a tendency to react with a wider variety of lymphocytes and to present higher titers than positive sera from the other groups tested.

Animals↗
PubMed1987

Effects of tumour necrosis factor and related cytokines on vascular endothelial cells.

Tumour necrosis factor (TNF) and related cytokines have been found to alter the phenotype of vascular endothelial cells so as to promote coagulation, inflammation and immunity. We have used recombinant human TNF, lymphotoxin (LT), interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta) to study and compare the effects of these molecules on cultured human endothelial cells (HEC). All four mediators cause HEC monolayers to reorganize from an epithelioid to a fibroblastoid morphology. Reorganization is slow (days), reversible upon cytokine withdrawal and enhanced by co-addition of immune interferon. Coincident with morphological change, TNF and LT (but not IL-1 alpha or IL-1 beta) cause a marked increase in HLA-A, B mRNA and antigen expression. TNF and LT also induce a slow increase in the mRNA levels and cell-surface expression of IL-1 species. All four cytokines have been reported to enhance HEC adhesiveness for lymphocytes and inflammatory leucocytes; these changes temporally coincide with a rapid (hours) and sustained increase in expression of intercellular adhesion molecule 1 (ICAM-1), and with a rapid but transient de novo expression of an endothelial-leucocyte adhesion molecule (detected by antibody H4/18), respectively. TNF and LT induce reciprocal tachyphylaxis for the reinduction of H4/18 binding but do not inhibit induction by IL-1 alpha and IL-1 beta; similarly, IL-1 alpha and IL-1 beta induce reciprocal tachyphylaxis but do not inhibit TNF or LT. We have used the binding of H4/18 to explore the mechanism of action of TNF. Tumour-promoting phorbol esters, but not agents which increase cytoplasmic calcium concentrations, were found to induce binding, suggesting a possible involvement of the protein kinase C pathway in the response of HEC to TNF. Cells pretreated for 24 hours with phorbol esters cannot be reinduced to express H4/18 binding by phorbol esters yet retain full responsiveness to TNF. Thus TNF also appears to act on HEC through a pathway independent of protein kinase C activation. Collectively, these effects of TNF and related cytokines may be understood as examples of endothelial cell activation.

Blood Coagulation↗
PubMed1987

Lymphotoxin: cloning, regulation and mechanism of killing.

The gene for murine lymphotoxin (MuLT) has been cloned from a cDNA library prepared using poly(A)+ RNA from an activated murine IL-2-maintained cloned T cell line (21C11). This was accomplished with a MuLT BamHI fragment isolated from a murine genomic library by hybridization to a human LT cDNA probe. Northern blot analysis with RNA from 21C11, an L3T4+ (CD4+-equivalent) ovalbumin-specific class II-restricted T cell line, revealed a 15S band that hybridized to this MuLT fragment. A cDNA library prepared with poly(A)+ RNA from 21C11 cells contained 36 colonies that hybridized with the MuLT BamHI fragment. A full-length cDNA has been isolated, sequenced, expressed in COS-1 cells and used to map MuLT to mouse chromosome 17. The sequence and structure of the MuLT gene has been determined. MuLT cDNA has been used to analyse mRNA expression in several L3T4+ and Lyt-2+ (CD8+-equivalent) T cell clones activated with antigen, mitogen, or antibody to the T cell receptor. LT is expressed by both class I- and class II-restricted T cells. The mechanism of killing by both LT and the functionally related molecule TNF-alpha includes the induction of DNA fragmentation in the target cell.

Animals↗
PubMed1995

Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-alpha by HLA-DR2+ T cells.

Lymphotoxin (LT) and tumor necrosis factor-alpha (TNF-alpha) play an important role in the pathogenesis of multiple sclerosis (MS). MS is associated with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. Because both LT and TNF-alpha are encoded in the HLA region, the HLA association of MS may be related to the production of these cytokines. To test this hypothesis, we investigated the production of LT, TNF-alpha, and interferon-gamma (IFN-gamma) by CD4+ T-cell lines (TCLs) specific for myelin basic protein (MBP) or tetanus toxoid (TT) isolated from MS patients and normal controls. After stimulation with specific antigen but not mitogen, TCLs from HLA-DR2+ donors produced significantly more LT and TNF-alpha than TCLs from DR2- donors. In contrast, HLA-DR2+ and DR2- TCLs did not differ in the production of IFN-gamma, a cytokine also produced by T cells but not encoded in the HLA region. Increased secretion of LT and TNF-alpha was unrelated to the specificity (MBP vs TT), MHC restriction (HLA-DR2 vs other DR molecules), or source (MS vs normal) of the TCLs. There was no significant association of the cytokine production with individual LT or TNF-alpha alleles, indicating that the increased production of these cytokines may be linked to other polymorphic genes in this region. The results suggest that the association of MS with HLA-DR2 implies a genetically determined propensity of T cells to produce increased amounts of LT and TNF-alpha.

Animals↗
PubMed1989

The presence of antibodies to lymphotoxin and tumor necrosis factor in normal serum.

Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytokines that probably play a role in several autoimmune diseases. In this report, we describe the detection, in normal nonimmune serum, of naturally occurring antibodies that bind to recombinant human LT and TNF. The naturally occurring antibodies that bind to LT and TNF could explain why normal immunoglobulin is effective therapy in idiopathic thrombocytopenic purpura and Kawasaki syndrome.

Animals↗
PubMedDate not supplied

Nature of cold-reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus.

Antilymphocyte antibodies in serum from patients with systemic lupus erythematosus (SLE), as detected by microcytotoxicity and indirect immunofluorescence, were predominantly cold reactive and of the IgM class. These IgM antibodies were most active at 4 degrees C. IgG antibodies were infrequent, and were only minimally lymphocytotoxic. Most sera were cytotoxic for autologous lymphocytes and were equally reactive with normal and SLE lymphocytes, as well as with B- and T-cell preparations. Separate T- and B-cell specificities, which appeared not to be related to HL-A determinants, were identified by differential absorption experiments. The functional significance of these antilymphocyte antibodies is discussed.

Animals↗
PubMedDate not supplied

Association of cold-reactive antilymphocyte antibodies with lymphopenia in systemic lupus erythematosus.

In a prospective study 26 of 29 patients with systemic lupus erythematosus had cold-reactive antilymphocyte antibodies cytotoxic for autologous lymphocytes and lymphocytes from normal subjects. The level of antilymphocyte antibodies was highly correlated, by linear regression analysis, with lymphopenia in these patients. The data suggested that both the avidity and the concentration of these antibodies were important determinants in this relationship. A clear association between increased antilymphocyte antibody activity and exacerbation of SLE was demonstrated. Apart from lymphopenia, however, neither type of clinical manifestation nor any particular serologic abnormality appeared to be related to the presence of antilymphocyte antibodies.

Antibodies↗
PubMedDate not supplied

Lymphocytotoxic antibody activity in cryoprecipitates from serum of patients with SLE.

Complement-dependent cytotoxic activity against normal human peripheral blood lymphocytes was detected in 11 of 17 cryoprecipitates from the serum of patients with systemic lupus erythematosus (SLE). The lymphocytotoxicity was eliminated by treatment with 2-mercaptoethanol and iodoacetamide, and it was inhibited by antibody to human IgM but not anti-IgG. The titers of lymphocytotoxic activity in the cryoprecipitates were roughly proportional to the corresponding serum titers, but when they were normalized for IgM concentration it was apparent that selective concentration of lymphocytotoxic antibody occurred in the cryoglobulins. The relationship between cryoprecipitable lymphocytotoxicity and a number of laboratory and clinical parameters of SLE was studied. The amount of protein in the cryoprecipitates, which was greatest in patients with significant renal disease, correlated with a reduction of serum complement and the amount of antibody to DNA. However the lymphocytotoxic activity of the cryoglobulins did not correlate with the severity of SLE. The titer of lymphocytotoxic antibody was independent of a) the presence or absence of active lupus nephritis, b) the total protein or immunoglobulin content of the cryoprecipitates, c) serum complement levels, and d) the amount of circulating antibody to DNA. These findings cast doubt upon the pathogenetic significance of cryoprecipitable lymphocytotoxic antibody.

Antibodies↗
PubMed1981

Lymphokine-mediated suppression of chondrocyte glycosaminoglycan and protein synthesis.

Spontaneously released and T cell mitogen augmented lymphokine produced by human mononuclear cells has been shown to induce a concentration dependent reversible suppression of chondrocyte glycosaminoglycan and protein synthesis without significantly enhancing chondrocyte catabolic activity. The modulatory factor(s) is of T cell origin and is trypsin, pronase, and heat sensitive. Prostaglandin inhibitors failed to influence factor formation or activity. Although eluting from Sephadex G-100 over a wide range, peak activity had an approximate molecular weight of 53,000 and appeared distinct from recognized forms of lymphotoxin.

Amino Acids↗
PubMed1990

Effects of tumor necrosis factor alpha and beta on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes.

We examined the effects of recombinant human tumor necrosis factor (TNF) on human articular cartilage and chondrocytes in culture. Both TNF alpha and TNF beta stimulated cartilage matrix breakdown during prolonged culture and elevated the levels of plasminogen activator (PA) activity in both the supernatants and cell layers of cultured chondrocytes. Characterization of the PA activities by immunochemistry and by zymography following gel electrophoresis indicated that human chondrocytes produce both urokinase-type PA and tissue-type PA in response to TNF. The addition of both interleukin-1 and TNF alpha or TNF beta to chondrocyte cultures demonstrated a synergism between these cytokines in the generation of PA activity in the culture supernatants and cell layers. Our results suggest that both activated lymphocytes and monocytes may contribute to the cartilage destruction of inflammatory arthritis through their stimulation of chondrocytes with TNF beta and TNF alpha, respectively. Since PA is the only neutral proteinase reported to be elevated in TNF-stimulated chondrocyte cultures, it could have an important role in TNF-mediated cartilage destruction.

Cartilage, Articular↗