Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O75191 (H. influenzae)
 4,961 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines at an inflammatory site may be a better indicator of the clinical severity of an infectious disease than the serum levels of the cytokines. Concentrations of interleukin-1 beta (IL-1 beta) in paired samples of cerebrospinal fluid (CSF) from 10 rabbits with experimental bacterial meningitis caused by H. influenzae type b, were measured, and compared to the concentrations of four cytokines; IL-1 beta, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in CSF samples from 45 children with or without meningitis. The IL-1 beta concentrations in the CSF from rabbits with experimental meningitis were significantly higher than the concentrations in control animals without meningitis (p < 0.001). The mean CSF concentrations of IL-8 from meningitic children were significantly higher than in the control group without meningitis (p < 0.005). TNF-alpha was only detected in septic meningitis. Assays of IL-6, however, were not significantly different in the septic meningitis group, the aseptic meningitis group and the non-meningitis group. These data indicate a possible role of IL-1 beta, IL-8 and TNF-alpha as mediators in the meningeal inflammatory process in patients with meningitis and TNF-alpha, in particular, may play a role in the pathogenesis of septic meningitis.
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PMID:Concentrations of interleukin-1 beta, interleukin-6, interleukin-8 and TNF-alpha in cerebrospinal fluid from children with septic or aseptic meningitis. 130 8

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

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

We have previously shown that tonsil tissue both from children with tonsillar hypertrophy and recurrent tonsillitis is colonized and invaded by Haemophilus influenzae and Streptococcus pyogenes group A. In order to evaluate if these bacteria are involved in the immunopathogenesis of these two conditions, tonsillar cells from both groups were stimulated in vitro with intact, heat-inactivated H. influenzae or S. pyogenes A. The immunoreactivity was evaluated by assessing the induction of cytokine production (IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, IL-2, IFN-gamma, IL-4, TNF-beta and IL-10), which was detected at the single-cell level. All cytokines studied except IL-4 were induced in both groups after stimulation with H. influenzae or S. pyogenes A. The dominating cytokines were IL-1 beta, IFN-gamma and TNF-beta. No major differences in the cytokine pattern or number of cytokine-producing cells were noticed between the two patient cohorts after H. influenzae stimulation. Activation by S. pyogenes A bacteria gave rise to higher frequencies of IFN-gamma- and TNF-beta-synthesizing cells in the recurrent tonsillitis group. The incidence of CD4-, CD8-positive T cells and CD40-positive B cells was comparable between the two groups while the MAC-387-positive macrophages were significantly higher in the recurrent tonsillitis groups. In conclusion, a Th1 type of cytokine response was found in both groups following stimulation with H. influenzae or S. pyogenes A.
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PMID:Haemophilus influenzae and Streptococcus pyogenes group A challenge induce a Th1 type of cytokine response in cells obtained from tonsillar hypertrophy and recurrent tonsillitis. 951 80

Nontypeable Hemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined, but they may involve activation of NF-kappa B, a transcriptional activator of multiple host defense genes involved in immune and inflammatory responses. Here, we show that NTHi strongly activates NF-kappa B in human epithelial cells via two distinct signaling pathways, NF-kappa B translocation-dependent and -independent pathways. The NF-kappa B translocation-dependent pathway involves activation of NF-kappa B inducing kinase (NIK)--IKK alpha/beta complex leading to I kappa B alpha phosphorylation and degradation, whereas the NF-kappa B translocation-independent pathway involves activation of MKK3/6--p38 mitogen-activated protein (MAP) kinase pathway. Bifurcation of NTHi-induced NIK-IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase pathways may occur at transforming growth factor-beta activated kinase 1 (TAK1). Furthermore, we show that toll-like receptor 2 (TLR2) is required for NTHi-induced NF-kappa B activation. In addition, several key inflammatory mediators including IL-1 beta, IL-8, and tumor necrosis factor-alpha are up-regulated by NTHi. Finally, P6, a 16-kDa lipoprotein highly conserved in the outer membrane of all NTHi and H. influenzae type b strains, appears to also activate NF-kappa B via similar signaling pathways. Taken together, our results demonstrate that NTHi activates NF-kappa B via TLR2-TAK1-dependent NIK--IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase signaling pathways. These studies may bring new insights into molecular pathogenesis of NTHi-induced infections and open up new therapeutic targets for these diseases.
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PMID:Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKK alpha /beta-I kappa B alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. 1143

We investigated the role of cytokines in differences in histopathologic changes in the lung between bronchopneumonia caused by non-encapsulated Haemophilus influenzae strain 770235f(0)b(0)and systemic disease caused by type b H. influenzae strain 770235f(0)b(+). Tumour necrosis factor-alpha (TNF-alpha), interleukin-(IL)-6 and IL-1 beta levels in bronchoalveolar lavage fluid (BALF) samples of mice infected with strain 770235f(0)b(0)were higher than in those infected with strain 770235f(0)b(+)until 24 h post-infection. Serum IL-6 rapidly increased in strain 770235f(0)b(0)infection after 72 h post-infection. Serum TNF-alpha level in strain 770235f(0)b(0)infection appeared earlier than in strain 770235f(0)b(+)infection. IL-1 beta production in strain 770235f(0)b(+)infection was later than in strain 770235f(0)b(0)infection. Moreover, a biphasic concentration pattern of TNF-alpha and IL-6 was noted in BALF of mice with strain 770235f(0)b(0)infection.
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PMID:Lipoolygosaccharide indirectly enhances inflammatory lesions in lungs as a primary infection site by non-encapsulated and type B Haemophilus influenzae through production of cytokines. 1155 87