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)

Haemophilus influenzae and Streptococcus pneumoniae are common causes of respiratory tract infections. H. influenzae attach to receptor epitopes in mucins and in epithelial cell membranes. Attachment is followed by an epithelial cell cytokine response. Secreted cytokines then initiate inflammation, upset the integrity of the mucosal barrier, and lead to disease. S. pneumoniae do not bind to mucins but attach to respiratory tract epithelial cells. Attachment is increased by viral infection of the epithelial cells. Unlike H. Influenzae, S. pneumoniae induce apoptosis in epithelial cells, thus disrupting the mucosal barrier. Attachment and persistence is counterbalanced by antiadhesive as well as bactericidal molecules in secretions such as human milk. These examples illustrate the balance between host defenses and microbial virulence as it has coevolved to maintain the health of the respiratory mucosa.
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PMID:Aspects on the interaction of Streptococcus pneumoniae and Haemophilus influenzae with human respiratory tract mucosa. 887 40

In patients with cystic fibrosis (CF), respiratory tract infections caused by Staphylococcus aureus and Haemophilus influenzae are followed by Pseudomonas aeruginosa with increasing age. Chronic endobronchial lung infection with P. aeruginosa is the leading cause of morbidity and mortality. In Danish CF patients we noted that both onset of initial colonization and chronic lung infection with P. aeruginosa peaked during the winter months which is the season for respiratory virus infections. Virus may therefore pave the way for P. aeruginosa. We established a chronic P. aeruginosa lung infection in rats by embedding mucoid bacteria in seaweed alginate and installing the beads intratracheally into the lower part of the left lung. Although the rats did not suffer from CF, the antibody responses and the pathologic changes of the lungs mimicked the findings in CF patients. By using this model in normal and athymic rats we showed that the T-cell response during the "natural" course of the infection played no major role. In a model of acute P. aeruginosa pneumonia we found that the macroscopic inflammatory response of the lungs was immense and that the natural capacity to clear P. aeruginosa was very efficient and could not be improved by immunization, although high serum levels of IgM, IgG and IgA antibodies to P. aeruginosa alginate, LPS, exotoxin A and sonicate were induced. We developed a method for collecting and measuring IgA in saliva and noted that mucosal IgA antibodies were induced by vaccination; they did not significantly prevent inflammation, however. In the chronic rat model we succeeded to improve the survival significantly and to change the inflammatory response subsequent to vaccination from an acute type inflammation dominated by polymorphonuclear leukocytes (PMNs) as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. Furthermore, we found that rats immunized with an alginate containing vaccine had a significantly earlier cellular shift to a chronic type inflammation as well as a significant reduction in the severity of the macroscopic inflammation compared to two other vaccine groups and to nonimmunized controls. Similar results were obtained in rats treated with the TH1 cytokine, interferon-gamma (IFN-gamma). Several authors have shown that the lung tissue damage during chronic infection in CF patients is caused by a type III hypersensitivity reaction leading to release of elastase by PMNs surrounding the bacterial microcolonies. The cellular shift we have induced by vaccination and by IFN-gamma treatment therefore offers a possible new strategy for improving the clinical course in chronically infected CF patients.
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PMID:Potential of preventing Pseudomonas aeruginosa lung infections in cystic fibrosis patients: experimental studies in animals. 894 52

Effective induction of the specific mucosal immunity against the outer membrane protein P6 of Haemophilus influenzae was investigated. Twenty-four BALB/c mice were intranasally immunized with P6, twice, with 2 weeks in between, with or without intranasal cytokine treatment. The intranasal immunization evoked both anti-P6 specific mucosal IgA immunity and systemic IgG immunity. In addition, intranasal administration of rIL-2 and rIL-5 enhanced anti-P6 specific immune response was maintained for 3 weeks after the final immunization with the intranasal cytokine treatment. These suggest the possibility of intranasal immunization and the advantage of intranasal administration of cytokines for eliciting both mucosal and systemic immunity.
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PMID:Study on specific mucosal immunity by intranasal immunization of outer membrane protein P6 of Haemophilus influenzae with cholera toxin B subunit. 908 65

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

An immunoregulatory mechanism involving release of neutralizing autoantibodies (Aabs) to self cytokines during bacterial infections is presented herein. Intraperitoneal inoculation of Haemophilus influenzae type b into Sprague-Dawley rats resulted in a self-limiting meningitis. High levels of cells expressing mRNA for gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) were detected 12 to 48 h postinoculation (p.i.) in splenocytes, and large numbers of IFN-gamma-secreting cells were present in the spleen on day 3 p.i. These levels were undetectable at days 9 and 14 p.i. Increased titers of Aabs of immunoglobulin G (IgG) isotypes to both cytokines were observed, with a peak at day 7 p.i. and with very low levels at day 30. Upon reinoculation with H. influenzae type b at day 30, regeneration of Aabs was recorded 7 days later (i.e., at day 37). To elucidate their regulatory importance, Aabs dose-dependently inhibited IFN-gamma production by splenocytes, IFN-gamma-induced major histocompatibility complex expression by peritoneal macrophages, and TNF-alpha-induced thymocyte proliferation. To control the specificity of these Aabs, Fab fragments of purified serum Igs from day p.i. exhibited binding and neutralizing effects. Furthermore, preincubation of the sera with a cytokine inhibited the binding and neutralization effects of that particular cytokine, but not those of any other cytokine. Aab-producing B cells were cloned, and their supernatants had similar effects. Our data suggest a role for autoimmunity in cytokine regulation and suggest that a maintained balance of this mechanism may protect from sequelae.
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PMID:Potential role of autoantibodies in the regulation of cytokine responses during bacterial infections. 923 90

Using in situ hybridization with radiolabelled oligonucleotide probes, we studied the mRNA expression of IL-1beta, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma), and transforming growth factor-beta (TGF-beta) in the brain during the lethal course of experimental meningitis in a rat model inoculated intracisternally with Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae and in uninfected control rats inoculated with the same volume of PBS. The production of IL-1beta, IL-4, IL-6 and IFN-gamma was also evaluated by immunohistochemistry. In the brain of Hib-inoculated rats, there was marked mRNA expression of IL-1beta, IL-6, TNF-alpha, IL-12 and IFN-gamma. IL-1beta, IL-6 and TNF-alpha were up-regulated throughout the observation period at 2, 8 and 18 h post-inoculation (p.i.), with similar patterns of induction. The Th1 cytokines IFN-gamma and TNF-beta were up-regulated within 8 h p.i. IL-10 and TGF-beta were down-regulated at 18 h p.i., while IL-4 was not detected. In contrast, the brain of S. pneumoniae-inoculated rats showed lower levels of IL-1beta, IL-6 and TNF-alpha, but higher levels of TNF-beta and detectable mRNA expression of IL-4 when compared with Hib-inoculated rats. IL-12, IFN-gamma, IL-10 and TGF-beta exhibited similar patterns of induction in the brains of Hib- and S. pneumoniae-inoculated rats. At 18 h p.i., immunohistochemistry showed similar patterns of IL-1beta, IL-4, IL-6 and IFN-gamma as mRNA expression in the brains of Hib- and S. pneumoniae-inoculated rats. The differences of cytokine profiles induced by the two bacterial strains may imply that different immunomodulating approaches should be considered, depending on etiology.
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PMID:Haemophilus influenzae and Streptococcus pneumoniae induce different intracerebral mRNA cytokine patterns during the course of experimental bacterial meningitis. 927 17

Interleukin-10 (IL-10) is a cytokine with antiinflammatory effects. In a rabbit model of meningitis, IL-10 was given intracisternally or intravenously to evaluate the impact on inflammation induced by lipooligosaccharide (LOS), Haemophilus influenzae type b (Hib), or Listeria monocytogenes. Intracisternal IL-10 in concentrations >1 microg significantly reduced tumor necrosis factor-alpha (TNF-alpha) and lactate values in cerebrospinal fluid (CSF). Intravenous IL-10 (1 mg/kg) in two doses after intracisternal LOS significantly reduced CSF TNF-alpha and lactate. When Hib was used, animals were treated with ceftriaxone and dexamethasone with or without IL-10 (1 mg/kg). TNF-alpha was significantly reduced in animals treated with IL-10, dexamethasone, or both compared with levels in rabbits receiving ceftriaxone alone. Comparable results were obtained when L. monocytogenes was inoculated and animals were treated with ampicillin with or without IL-10, dexamethasone, or nothing. In conclusion, IL-10 modulates CSF TNF-alpha concentrations in experimental LOS, Hib, or L. monocytogenes meningitis. The maximal inhibitory effect was seen when IL-10 and dexamethasone were combined.
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PMID:The effect of interleukin-10 on meningeal inflammation in experimental bacterial meningitis. 935 24

Intraperitoneal inoculation of Haemophilus influenzae type b (Hib) to 3-week-old Sprague-Dawley rats resulted in nonlethal meningitis with high levels of leukocytes in the cerebrospinal fluid (CSF) and positive bacterial culture. Using in situ hybridization, levels of cytokine mRNA-expressing cells were determined in the brain, CSF, and spleen from Hib-inoculated and uninfected control rats. IFN-gamma, IL-1 beta, IL-4, IL-6, IL-10, IL-12, and TNF-alpha mRNA levels were elevated at 12 hr postinoculation (pi) in spleen and CSF. At this time point, strong expression of IL-6 and TGF-beta was detected in the brain, and also of IL-10 at 48 hr while IFN-gamma and IL-12 were expressed at very low levels throughout the observation time. Delayed cytokine induction occurred in CSF compared to spleen and brain. TGF-beta was high in CSF at 48 hr, and some elevation of IL-1 beta, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-12 was evident at 72 hr pi. This may suggest measures that promote production of TGF-beta and/or IL-10 should be evaluated in treatment of bacterial meningitis.
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PMID:Cytokine mRNA profiles during the course of experimental Haemophilus influenzae bacterial meningitis. 940 Jun 23

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

We have recently described the induction of anti-cytokine autoantibodies (Aabs) in the serum as a novel mechanism for cytokine regulation during bacterial infections. Here we use the infant rat-model of Haemophilus influenzae type b (Hib) meningitis to examine the induction of five potentially important cytokines and their autoantibody responses in the CSF. Protein levels of the cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-4 and IL-10 were detected at day 3 post-inoculation (p.i.) with maximum induction at day 8. Thereafter, these levels of cytokines had become undetectable. Increased Aab titres to these cytokines, except IL-4, were registered with peak levels between days 7 and 9. Upon re-inoculation with Hib at day 30, regeneration of Aabs was recorded 7 days later (i.e. at day 37). To control the specificity of these Aabs, preincubation of the CSF with a cytokine inhibited the binding effects of that particular cytokine, but not those of any other cytokine. Aabs dose-dependently inhibited IFN-gamma-induced MHC expression by peritoneal macrophages and TNF-alpha-mediated L929 cytotoxicity. Our data demonstrate for the first time the existence of the anti-cytokine antibodies in the CSF of the meningitis Hib model. Furthermore, the data present a role for the Aabs in cytokine regulation, which is consistent with the previously demonstrated effects of the Aabs in the serum.
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PMID:Induction of cytokines and anti-cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis. 984 49


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