Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukins have been recognized as potential adjuvants for use during vaccination. The immunogenicity of some poorly immunogenic bacterial capsular polysaccharides have been improved by conjugation to a protein carrier. Augmentation of the immune response to these glycoconjugates, however, may be realized in the presence of interleukins. The antibody response to one such vaccine which comprises a oligosaccharide derived from the capsule of Haemophilus influenzae type b coupled to CRM197 (HbOC) can be augmented in this manner. A suboptimal dose (0.1 microgram) of HbOC and varying concentrations of IL-1 alpha or IL-1 beta (10(2) - 5 x 10(5) U) were injected intramuscularly at 0 and 2 weeks into Swiss Webster mice. Vaccines were also formulated with and without aluminum phosphate. Antibody to the oligosaccharide was determined by Farr assay. In 3/3 experiments, IL-1 alpha enhanced primary and secondary antibody responses whereas with IL-1 beta, only a slight increase in the primary antibody response was seen but enhanced secondary responses were observed. Thus, IL-1 alpha and to some extent IL-1 beta enhanced the primary and secondary antibody responses to a glycoconjugate vaccine.
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PMID:Augmentation by interleukins of the antibody response to a conjugate vaccine against Haemophilus influenzae b. 180 64

Because Haemophilus influenzae type b (Hib) is the principal cause of suppurative arthritis in young children and its lipooligosaccharide (LOS) is thought to be the main virulence factor, Hib endotoxin was evaluated for its ability to induce synovial inflammation in rabbits. Also, the role of the cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) in mediating the synovial inflammatory process was studied. Intraarticular inoculation of 2 pg to 20 ng of Hib LOS produced a dose-dependent increase in concentrations of leukocytes and protein in synovial lavage fluid that was significantly modulated by concomitant administration of rabbit TNF alpha- and rabbit IL-1 beta-specific antibodies. Inoculation of joints with either 10(4) IU of rabbit TNF alpha or 10 ng recombinant rabbit IL-beta induced synovial inflammatory changes similar to those observed after LOS intraarticular challenge. These data provide evidence for the role of Hib LOS in inducing suppurative arthritis and for the critical participation of TNF alpha and IL-1 beta in the initial events of the synovial inflammatory response.
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PMID:Induction of suppurative arthritis in rabbits by Haemophilus endotoxin, tumor necrosis factor-alpha, and interleukin-1 beta. 203 91

Although antibiotics have reduced mortality, the most recent clinical trials in sepsis and meningitis have been directed at the host inflammatory response in an attempt to improve outcome. Endotoxin, cell wall constituents and toxins are potent inducers of small molecular weight proteins (cytokines) from a variety of host cells. Several lines of investigation have implicated tumor necrosis factor-alpha (TNF-alpha) as a cytokine mediator of sepsis and septic shock. A recent study has been able to measure plasma TNF-alpha concentrations in patients with meningococcemia and demonstrated a correlation with prognostic groups related to mortality. Therefore, TNF-alpha, probably through its effects on other mediators, has an effect in sepsis. New speculation regarding morbidity in bacterial meningitis focuses on cytokine activity in the central nervous system. Cerebrospinal fluid (CSF) from experimental animals with meningitis contains increased amounts of interleukin-1 beta (IL-1 beta) and TNF alpha. These IL-1 beta levels correlated directly with duration of fever and neurological sequelae. Children with Haemophilus influenzae, type b meningitis treated with dexamethasone had significantly reduced levels of CSF IL-1 beta compared to placebo-treated controls.
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PMID:The immunology of sepsis and meningitis--cytokine biology. 209 Dec 57

Pentoxifylline has been shown to decrease endotoxin-induced tumor necrosis factor alpha production and reverse the inflammatory actions of interleukin-1 (IL-1) and tumor necrosis factor on leukocyte function. Because of the potential role of this cytokine-leukocyte interaction in the pathogenesis of bacterial meningitis, we investigated the ability of pentoxifylline to modulate meningeal inflammation in the rabbit meningitis model. Pentoxifylline treatment (initially an intravenous injection of 20 mg/kg followed by 6 mg/kg per h) started 20 min before intracisternal injection of 20 ng of Haemophilus influenzae type b lipooligosaccharide (endotoxin) reduced significantly concentrations in cerebrospinal fluid of leukocytes (P less than 0.0001), protein (P less than 0.001), and lactate (P less than 0.001) during the 9-h infusion compared with values in intravenous-saline-treated rabbits. When pentoxifylline was given 1 h after H. influenzae type b endotoxin, the mean peak lactate and leukocyte concentrations in cerebrospinal fluid were significantly lower than those in control animals. Pentoxifylline also significantly decreased lactate and protein concentrations (P less than 0.05) and tended to diminish leukocyte counts (P = 0.08) compared with results in control animals after antibiotic-induced release of endotoxin in animals with H. influenzae meningitis. In this regard, dexamethasone was superior to pentoxifylline and no synergism was observed when the drugs were combined. Additionally, pentoxifylline attenuated meningeal inflammatory changes induced by intracisternal inoculation of 10 ng of rabbit recombinant IL-1 beta compared with results in either dexamethasone- or saline-treated animals. We conclude that pentoxifylline is effective in this animal model in modulating the meningeal inflammatory response following intracisternal inoculation of H. influenzae type b endotoxin or organisms or rabbit recombinant IL-1beta.
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PMID:Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis. 236 Aug 22

Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the meningeal inflammatory cascade, the results obtained by several groups of investigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta). Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrIL-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-alpha and IL-1 beta in the initial events of meningeal inflammation.
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PMID:Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. 237 90

Murine macrophages of the P388D1 cell line stimulated with lipopolysaccharide (LPS) from Haemophilus actinomycetemcomitans Y4 released an interleukin-1 (IL-1) inhibitor, as well as IL-1. Maximal IL-1 activity in culture supernatants was detected after 24 h of culture. On the other hand, IL-1 inhibitor activity reached a maximum level after 72 h of culture. An IL-1 inhibitor was partially purified from the culture supernatant of P388D1 cells stimulated with Y4 LPS for 72 h by ammonium sulfate precipitation, followed by Sephacryl S-200 gel chromatography. A 160-kilodalton peak inhibitory to IL-1 and a 14-kilodalton peak showing IL-1 activity were separated by Sephacryl S-200 column chromatography. The partially purified IL-1 inhibitor significantly suppressed the proliferation of C3H/HeJ murine thymocytes that had been induced with murine and human IL-1 in the presence of a submitogenic dose of concanavalin A. The IL-1 inhibitor more strongly suppressed human recombinant IL-1 beta than human recombinant IL-1 alpha. This inhibitory activity of the partially purified preparation was unaffected by the presence of trypsin inhibitor and the protease inhibitor aprotinin. The IL-1 inhibitor did not exhibit either IL-2 or IL-2 inhibitor activity. The inhibitor suppressed C3H/HeJ thymocyte proliferation induced by IL-1 in the presence of a saturated concentration of IL-2 instead of a suboptimal concentration of concanavalin A. These results indicate that prolonged culture of Y4 LPS-stimulated murine macrophages releases a specific inhibitor of IL-1.
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PMID:Production of an interleukin-1 inhibitor by cell line P388D1 murine macrophages stimulated with Haemophilus actinomycetemcomitans lipopolysaccharide. 326 86

The effects of dexamethasone, pentoxifylline, and MAb against endotoxin (HA-1A) on the release of various proinflammatory mediators, i.e. tumor necrosis factor-alpha (TNF), IL-1 beta, IL-8, and prostaglandin 2, by human leukocytes during stimulation with Haemophilus influenzae type B were studied. The results show that only monocytes, and thus neither lymphocytes nor granulocytes, release these mediators in response to H. influenzae. Dexamethasone inhibited the release of all of these mediators, whereas pentoxifylline only inhibited the release of TNF. HA-1A only reduced the release of IL-8 from adherent monocytes significantly and had no significant effect on the release of TNF, IL-1 beta, and prostaglandin E2. In whole blood, no significant effect of HA-1A on the release of TNF, IL-1 beta, IL-8, and prostaglandin E2 was found. In summary, the results of this study demonstrate that dexamethasone is the most potent inhibitor of the release of proinflammatory mediators by monocytes induced by H. influenzae type B.
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PMID:In vitro effect of dexamethasone, pentoxifylline, and anti-endotoxin monoclonal antibody on the release of proinflammatory mediators by human leukocytes stimulated with Haemophilus influenzae type B. 793 25

The host-parasite relationship in the nasopharynx of young children with bacterial colonization and antigen uptake in the mucosa and lymphatic tissue provides an opportunity to investigate infectious/inflammatory processes and responses. IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were analysed in nasopharyngeal secretions and serum from children with or without recurrent episodes of acute otitis media, from healthy adults and adults with or without recurrent episodes of acute otitis media, from healthy adults and adults with hypogammaglobulinaemia or selective deficiency of IgG3. Nasopharyngeal secretions generally contained substantial amounts of IL-1 beta, IL-6 and TNF-alpha. In contrast, IL-1 beta, IL-6 and TNF-alpha were not detectable in sera on the same occasion. Children were found to have higher levels of IL-1 beta, IL-6 and TNF-alpha than healthy adults and than adults with immunodeficiency. High levels of IL-1 beta were associated with low or undetectable levels of IL-6 and TNF-alpha, whereas the opposite pattern was seen in association with low levels of IL-1 beta. This was especially true for children with recurrent episodes of acute otitis media (RAOM). In children with nasopharyngeal colonization with Haemophilus influenzae, significantly higher levels of IL-1 beta, IL-6 and TNF-alpha (P = 0.0001, respectively) were found compared with non-colonized children. Notably, the RAOM children exhibited significantly lower levels of IL-1 beta, IL-6, and TNF-alpha in nasopharyngeal secretions (P = 0.0001, 0.01 and 0.0001, respectively) than healthy children. These results demonstrate local production of inflammatory cytokines in nasopharynx, related to bacterial colonization, and suggest that children with RAOM are poor nasopharyngeal cytokine producers.
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PMID:Cytokines in nasopharyngeal secretions; evidence for defective IL-1 beta production in children with recurrent episodes of acute otitis media. 808 94

A deregulated expression and/or release of large amounts of inflammatory cytokines such as IL-1 and TNF-alpha accounts for most pathophysiological events in a variety of systemic inflammatory diseases, the effect being mediated by the interaction of these cytokines with their respective receptors. IL-1 receptor antagonist (IL-1Ra), mainly produced by monocytes/macrophages, is an inhibitor of IL-1 activity. The present study shows that human serum IgA induces significant IL-1Ra release in human peripheral blood mononuclear cells and adherent monocytes. IgA induced higher levels of IL-1Ra than Haemophilus influenzae type b (Hib) expressing lipopolysaccharide (LPS), purified LPS or phorbol myristate acetate (PMA), without induction of IL-1 beta release, and even inhibited LPS-induced IL-1 beta release. Induction of IL-1Ra by IgA could be detected both at the mRNA and protein levels in resting and activated monocytes. Ligation of Fc alpha R with MoAb My-43 or treatment with human serum IgA induced protein tyrosine phosphorylation in human monocytes, and herbimycin A, a specific inhibitor of protein tyrosine kinase activity, inhibited IgA-induced IL-1Ra production, suggesting that Fc alpha R-mediated induction of tyrosine phosphorylation is required for the IgA-induced stimulation of IL-1Ra release. In addition, triggering of Fc alpha R with MoAb specifically down-regulated TNF-alpha and IL-6 release in human monocytes activated with Hib. By the induction of IL-1Ra and down-regulation of the release of inflammatory cytokines such as IL-1 beta, TNF-alpha and IL-6, interaction of IgA with human monocytes may actively contribute to the regulation of the inflammatory response.
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PMID:Anti-inflammatory properties of human serum IgA: induction of IL-1 receptor antagonist and Fc alpha R (CD89)-mediated down-regulation of tumour necrosis factor-alpha (TNF-alpha) and IL-6 in human monocytes. 880 46

The present study concerns the effect of the xanthine derivates lisofylline (LSF) and pentoxifylline (PTX) on the production of pro-inflammatory cytokines tumour-necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and the de-activating cytokine interleukin-10 (IL-10) by human leucocytes during stimulation with lipopolysaccharide (LPS), heat-killed Gram-negative bacteria (GNB) or Gram-positive bacteria (GPB). The production of TNF-alpha and IL-1 beta by leucocytes stimulated with LPS, Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae was inhibited by both drugs. The production of IL-10 by leucocytes stimulated with LPS and Hib was inhibited by both xanthine derivates only at 48 hr. However, incubation of leucocytes with S. pneumoniae in the presence of LSF or PTX stimulated the production of IL-10 about four- and twofold at 24 hr and 48 hr, respectively. In all instances, the extent of inhibition or enhancement of cytokine production by LSF or PTX was equal. The divergent effects of xanthine derivates on the IL-10 production indicate the existence of distinct intracellular pathways depending on whether leucocytes are stimulated by GPB or GNB.
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PMID:Effect of lisofylline and pentoxifylline on the bacterial-stimulated production of TNF-alpha, IL-1 beta IL-10 by human leucocytes. 922 16


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