Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:031927 (cytokine)
 144,509 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene product of the murine Steel (Sl) locus encodes an early-acting hematopoietic growth factor that is a ligand for the c-kit protooncogene. Several cDNAs for the Sl gene product, known as mast cell growth factor (MGF), stem cell factor (SCF), or kit ligand (KL), have recently been isolated, and both soluble and membrane-associated versions have been shown to be biologically active. The potential for therapeutic usage of recombinant MGF (rMGF) indicated a need for determining the biodistribution and elimination parameters of this cytokine. Pharmacokinetic studies demonstrated that radiolabeled rMGF had a distribution half-life of 2 min and an elimination half-life of 2.1 h in wild-type mice following iv injection, during which a striking localization of labeled rMGF in the lungs was noted. When administered by subcutaneous injection the elimination half-life was prolonged to 8.4 h. The primary sites of rMGF elimination appeared to be the kidneys and the liver. Pharmacokinetic analysis of labeled rMGF in mutant Sl/Sld mice, which are mast cell deficient, demonstrated similar distribution and elimination half-lives compared to wild-type mice (1.4 min and 1.8 h, respectively). In addition, the biodistribution pattern of the labeled rMGF in Sl/Sld mice was similar to that observed in wild-type mice, including the striking localization to the lungs. Binding of radiolabeled rMGF to lungs in vivo subsequent to iv injection was completely inhibited by excess unlabeled rMGF. Interestingly, mice that received an iv injection of the higher doses of rMGF (15 micrograms) demonstrated profound respiratory distress and hypotension within minutes of administration. Histologic analysis of lungs from such mice revealed extensive mast cell degranulation, which was associated with vasodilatation and pronounced hyperemia of virtually all pulmonary vessels. The respiratory distress in normal mice was probably a consequence of mast cell degranulation induced by rMGF since similar findings were not observed in Sl/Sld mice injected with identical concentrations of rMGF.
 ...
PMID:Pharmacokinetic parameters of recombinant mast cell growth factor (rMGF). 128 75

Candida albicans (CA) increasingly causes septic shock, acute lung injury, and multiple organ damage during immunosuppression-related neutropenia. However, the effects of neutrophil (PMN) depletion on induction of tumor necrosis factor-alpha (TNF) by CA and its potential mediation of Candida septic shock are unknown. We hypothesized that reduced CA uptake by circulating PMNs during cyclophosphamide (CY)-related neutropenia sensitizes to TNF-mediated shock from enhanced cytokine production after phagocytosis by tissue macrophages. Absolute or relative neutropenia (PMNs < or = 500/microliters or 2,500/microliters) was modeled in rats by intraperitoneal CY 4-8 days before 10(9) yeast-phase CA (acute studies < or = 24 h, n = 81 animals) or 10(6) CA (subacute studies < or = 72 h, n = 25). Compared with neutrophil-sufficient rats, absolute neutropenia accelerated hemodynamic collapse and respiratory distress after 10(9) CA, and pulmonary microvascular permeability was amplified. These changes evolved without increased candidemia or elevations in bioactive or antigenic serum TNF, which remained low even at death (42.3 +/- 14.8 U/ml vs. 12.6 +/- 2.9 U/ml for CY + saline, means +/- SE, P = NS). In contrast, significant TNF in lung tissue and bronchoalveolar lavage fluid (BALF) was evident within 6 h in CY + 10(9) CA rats. Electron microscopy confirmed hyphal proliferation into alveoli from yeast within mononuclear cells in lung capillaries. Subacute disseminated candidiasis after 10(6) CA was not associated with elevated serum, lung, or BALF TNF. We conclude that differential systemic and intrapulmonary TNF production occur in CA septic shock during preexisting neutropenia, with compartmentalized TNF production in the lower respiratory tract accompanying yeast-mycelial transformation. Thus TNF is not an obligate mediator of acute candidemic shock or subacute disseminated candidiasis during CY-induced immunosuppression but may initiate pulmonary injury accompanying high-grade candidemia.
 ...
PMID:Differential systemic and intrapulmonary TNF-alpha production in Candida sepsis during immunosuppression. 144 56

Transfusion-associated respiratory distress occurred more often in the past in Taiwan but recently only very rarely. From the results of our studies it would appear that the former cases did not represent immune reactions involving red blood cells, serum proteins (especially IgA), HLA or granulocyte-specific antigens. Other causes, such as improper handling of the blood units may have been involved, but further study is also needed to investigate the possibility of the role of cytokine release from leukocytes or other factors. In addition, it appears that both plasma and serum obtained by recalcification of plasma may cause false-positive reactions in the granulocyte microagglutination test.
 ...
PMID:Transfusion-associated respiratory distress in Taiwan. 770 8

Transfusion of blood components is usually required in the management of critically ill patients. However, pathologic interactions between blood products and organ function may result from transfusion reactions. Emerging understanding of the mediation and interruption of clinical inflammatory responses is applicable to severe transfusion reactions. The pathophysiology of four types of severe transfusion reactions are reviewed: a) acute hemolysis; b) bacterial contamination of blood components; c) transfusion-related acute lung injury (TRALI); and d) anaphylaxis. Acute hemolytic reactions are often caused by preventable errors in sample or patient identification. Renal toxicity, coagulopathy, and hypotension may result from circulating red cell stroma and immune-complex activation of complement and cytokine secretion. Bacterial contamination of blood components has caused patient sepsis in many cases; platelets stored at 20 degrees to 24 degrees C are of particular concern. Careful blood collection and handling is essential for prevention. TRALI is manifested by acute respiratory distress, which is usually caused by infusion of plasma containing antibodies against the patient's leukocytes. Complement activation and cytokine stimulation cause edema and neutrophil accumulation in the lungs. Anaphylactic reactions may result from patient immunoglobulin (Ig)E antibodies against donor plasma constituents. IgA-deficient patients are at risk for anaphylactic reactions if these patients develop anti-IgA antibodies. Vasoactive or complement-activating factors in a blood product may also cause anaphylactoid reactions in some patients.
 ...
PMID:The pathophysiology and organ-specific consequences of severe transfusion reactions. 780 6

The relaxing effects of nitric oxide on smooth muscles, first identified in 1987, inaugurated a new area of therapeutic efficacity in intensive care. Nitric oxide is synthesized by endothelial cells, macrophages, brain cells and other cells following immunological activation and plays a role in normal blood pressure homeostasis, neuromodulation, cytotoxicity and intracellular message transmission. Since inappropriate vasodilatation or shock may result from cytokine- or endotoxin-induced overproduction of nitric oxide, experiments have been conducted on the effect of nitric oxide synthase inhibitors on shock-induced hypotension. In animal models, results have demonstrated a new method for treating septic shock since infusing nitric oxide inhibitors can rapidly re-establish haemodynamics. Nevertheless, due to possible interference with the immune defense system further studies on the physiological, pharmacological and metabolic effects are required before routine antishock therapy can be used in the intensive care unit. Inversely, in pulmonary hypertension there may be an insufficient production of endogenous nitric oxide. Thus administration via inhalation would represent a promising replacement therapy. In addition, since nitric oxide is rapidly inactivated by haemoglobin, its vasodilatory effect is restricted to the pulmonary vasculature resulting in lowered pulmonary artery pressure without systemic vasodilatation. Effective protocols have been developed for primary pulmonary hypertension of the newborn and acute respiratory distress syndrome. The bronchodilatory effect of nitric oxide is another area suggesting an alternative approach to treating different causes of bronchoconstriction including asthma. The results of early clinical trials are awaited. When used in low concentrations under continuous monitoring, nitric oxide is a safe new therapeutic option for the treatment of pulmonary hypertension and nitric oxide inhibitors may have an important role to play in the management of septic shock.
 ...
PMID:Nitric oxide: a new area in intensive care. 793 7

T cells appear to play a central role in viral bronchiolitis, but the effects of different functional and phenotypic subgroups of T cells have not been defined. To test the activities of T cells recognizing individual proteins of respiratory syncytial (RS) virus, virus-specific T cell lines were produced from mice primed by scarification with recombinant vaccinia viruses expressing the major surface glycoprotein (G), fusion protein (F) or second matrix (22K) protein of RS virus. As previously reported, the in vitro characteristics of these cells are predetermined by the choice of RS virus protein: 22K-specific cells are predominantly class I-restricted cytolytic CD8+ cells; F-specific cells, a mixture of cytolytic CD8+ cells and CD4+ cells with a T helper 1 cell (Th1) cytokine secretion profile, whereas those from G-sensitized mice are almost exclusively CD4+, with Th2 characteristics. Mice infected intranasally with RS virus showed mild illness and recovered fully, but developed respiratory distress after intravenous injections of T cells. Dose-for-dose, infected mice receiving G-specific cells suffered the most severe (sometimes fatal) illness, characterized by lung hemorrhage, pulmonary neutrophil recruitment (shock lung) and intense pulmonary eosinophilia. This disease was further enhanced by coinjection of 22K-specific cells, which alone caused mild shock lung without eosinophilia. F-specific cells caused minimal enhancement of pathology and had little or no effect on the disease caused by G-specific cells. Each cell line reduced lung virus titer and combined injections of G- and 22K-specific cells eliminated infection completely. The in vitro characteristics of these antiviral T cell lines therefore predict the pathological effects in vivo. Moreover, different forms of viral bronchiolitis can be caused by functionally distinct types of activated T cell.
 ...
PMID:Distinct types of lung disease caused by functional subsets of antiviral T cells. 827 Aug 85

Multiple mediators have been implicated in the interactions between the liver and the lungs in various disease states. The best characterized mediator of liver-lung interaction is alpha 1-antitrypsin. Several cytokines and mediators may be involved in the pathogenesis of the hepatopulmonary syndrome and in the cytokine cascades that are activated in systemic inflammatory states such as acute respiratory distress syndrome. Hepatocyte growth factor or scatter factor is a recently described peptide with a broad range of biologic effects that may mediate lung-liver interactions.
 ...
PMID:Mediators, cytokines, and growth factors in liver-lung interactions. 866 87

Although the pathogenesis of the acute respiratory distress syndrome (ARDS) is complex and poorly understood, several observations point to an important role of interactions between polymorphonuclear neutrophils (PMN) and cytokines in this process. We therefore studied certain parameters involved in PMN transendothelial migration (adhesion molecule expression and cytoskeletal organization) in patients with ARDS (n = 14) in comparison with other ventilated patients (n = 15). We found that in the basal state, both whole-blood PMN and alveolar PMN obtained by bronchoalveolar lavage (BAL) were activated, as shown by decreased L-selectin CD62L and increased beta 2 integrin CD11b expression, as well as decreased F-actin content. The degree of PMN activation increased with the degree of lung injury and with the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Moreover, the capacity of ex vivo stimulation of alveolar PMN by a bacterial peptide was low in ARDS and could partly account for the high susceptibility of these patients to lung infection. Therefore, ARDS-associated lung injury could be caused, at least in part, by inappropriate adhesion and transendothelial migration of proinflammatory cytokine-primed PMN.
 ...
PMID:Interactions between neutrophils and cytokines in blood and alveolar spaces during ARDS. 881 May 92

To determine the relationship between airspace cytokines and cellular inflammatory responses in patients with the acute respiratory distress syndrome (ARDS), we performed bronchoalveolar lavage (BAL) in 82 prospectively identified, mechanically ventilated patients on Days 3, 7, 14, and/or 21 after the onset of ARDS. We studied the relationships between bronchoalveolar lavage fluid (BALF) cell populations and the concentrations of two potent neutrophil (PMN) chemoattractants, interleukin-8 (IL-8) and epithelial cell-derived neutrophil activator-78 (ENA-78); two potent monocyte chemoattractants, monocyte chemotactic peptide-1 (MCP-1) and macrophage inflammatory peptide-1 alpha (MIP-1 alpha); and the early response cytokine interleukin-1 beta (IL-1 beta) and its naturally occurring antagonist, IL-1 receptor antagonist protein (IRAP). We found that all of these cytokines were significantly increased regardless of the duration of ARDS. IL-8 and ENA-78 were the cytokines most strongly and consistently correlated with PMN concentrations in the lung fluids of patients with ARDS, and the correlations were independent of the other cytokines or coexisting lung infection. None of the cytokines tested correlated with macrophage concentrations. MCP-1 was directly correlated with lung injury score on Days 7, 14, and 21. Although neither IL-8 nor ENA-78 was associated with outcome, levels of IL-1 beta measured on Day 7 were associated with an increased risk of death (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.1 to 7.4). These data demonstrate potential molecular mechanisms of the persistent inflammatory process in the lungs of patients with ARDS.
 ...
PMID:Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. 881 May 93

Tumor necrosis factor-alpha (TNF-alpha)-induced inhibition of surfactant synthesis participates in the pathogenesis of the acute respiratory distress syndrome. We examined the ability of human type II pneumocytes to produce nitric oxide (NO) in the presence of TNF-alpha as well as the role of NO and prostaglandin (PG) E2 in the transduction of the cytokine signal. Multiple organ donors were used as a source of lung tissue. After 24-h preculture, type II pneumocytes were cultured for 18 h in the presence or absence of additives. The D-[U-14C] glucose incorporation into phosphatidylcholine (PC) was selectively inhibited by TNF-alpha, PGE2, sodium nitroprusside (SNP), or 8-bromoguanosine 3',5'-cyclic monophosphate. The effect of TNF-alpha was attenuated by indomethacin, N omega-nitro-L-arginine methyl ester (NAME), or methylene blue (MB). The effect of PGE2 was attenuated by NAME, while that of SNP was reversed by MB but not by indomethacin. TNF-alpha induced an increase in PGE2 and guanosine 3',5'-cyclic monophosphate cell content and in the NO release to the medium. NAME did not affect PGE2 production, while indomethacin blunted NO generation. Our results suggest that NO generation, secondary to PGE2 production, is responsible for the TNF-alpha-induced inhibition of PC synthesis by human type II pneumocytes.
 ...
PMID:TNF-alpha-induced inhibition of PC synthesis by human type II pneumocytes is sequentially mediated by PGE2 and NO. 884 83


1 2 3 4 5 6 7 8 9 10 Next >>