Induction of Phagocyte‐Stimulating Cytokines by <i>In Vitro</i> Stimulation of Human Peripheral Blood Mononuclear Cells with <i>Haemophilus influenzae</i>

Arvå, E; Åndersson, Bengt

doi:10.1046/j.1365-3083.1999.00480.x

Cited by 11 publications

(5 citation statements)

References 26 publications

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“…We could not detect any significant differences in the levels of inflammatory mediators between effusions yielding the Gram-positive S. pneumoniae or the Gram-negative H. influenzae, despite in vitro findings of different responses to these bacteria and to Gram-positives and Gram-negatives in general [10,11,26]. This shows that viable bacteria interacting with host tissue produce additional inflammatory stimuli to those provided by the bacterial structures themselves.…”

Section: Discussionmentioning

confidence: 56%

High cytokine levels in perforated acute otitis media exudates containing live bacteria

Skovbjerg

Roos²,

Nowrouzian

et al. 2010

Clinical Microbiology and Infection

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Acute otitis media (AOM) is an inflammatory response to microbes in the middle ear, sometimes associated with rupture of the tympanic membrane. Human leukocytes produce different patterns of inflammatory mediators in vitro when stimulated with Gram-positive and Gram-negative bacteria, respectively. Here, we investigated the cytokine and prostaglandin E2 (PGE2) responses in middle ear fluids (MEFs) from children with spontaneously perforated AOM, and related the mediator levels to the presence of pathogens detected by culture (live) or PCR (live or dead). Furthermore, the in vivo cytokine pattern was compared with that induced in leukocytes stimulated by dead bacteria in vitro. MEFs with culturable pathogenic bacteria contained more interleukin (IL)-1β (median: 110 μg/L vs. <7.5 μg/L), tumour necrosis factor (TNF) (6.3 μg/L vs. <2.5 μg/L), IL-8 (410 μg/L vs. 38 μg/L) and IL-10 (0.48 μg/L vs. <0.30 μg/L) than culture-negative fluids, irrespective of PCR findings. IL-6 and PGE2 were equally abundant (69-110 μg/L) in effusions with live, dead or undetectable bacteria. Cytokine levels were unrelated to bacterial species and to the presence or absence of virus. Similar levels of TNF and IL-6 as found in the MEFs were obtained by in vitro stimulation of leukocytes, whereas 11 times more IL-1β and 3.5 times more IL-8 were produced in vivo, and 22 times more IL-10 was produced in vitro. Vigorous production of proinflammatory cytokines accompanies AOM with membrane rupture, regardless of the causative agent, but the production seems to cease rapidly once the bacteria are killed and fragmented. IL-6 and PGE2, however, remain after bacterial disintegration, and may play a role in the resolution phase.

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Section: Discussionmentioning

confidence: 56%

High cytokine levels in perforated acute otitis media exudates containing live bacteria

Skovbjerg

Roos²,

Nowrouzian

et al. 2010

Clinical Microbiology and Infection

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“…Whether Gram-positive bacteria are generally better in stimulating IL-12 than Gram-negative bacteria remains to be tested. Support for this notion derives from the observation that Gram-positive staphylococci are much better stimulators of IL-12 than E. coli lipopolysaccharide (LPS) or mycobacteria [28] and that the Gram-positive pneumococci give rise to 30 times more IL-12 than the Gram-negative Haemophilus influenzae [29,30]. IL-12 enhances the cytotoxicity mediated by NK cells against tumours [17], which may be of relevance to the capacity of certain lactobacilli strains to promote anti-tumour functions in mice [9,31].…”

Section: Discussionmentioning

confidence: 99%

Lactobacilli from human gastrointestinal mucosa are strong stimulators of IL-12 production

Hessle

Hanson

Wold

1999

Clinical and Experimental Immunology

215

145

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SUMMARYInteraction of macrophages with bacteria is a stimulus for production of cytokines such as IL-10 and IL-12. IL-12 stimulates T cell and natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-g) production. IL-10 opposes the T cell-stimulating action of IL-12, decreases the release of proinflammatory cytokines from macrophages, and stimulates B cells. We have studied the capacity of human intestinal isolates from the three Lactobacillus species dominating on the human gastrointestinal mucosa, L. plantarum, L. rhamnosus and L. paracasei ssp. paracasei, to induce production of IL-10 and IL-12 from human blood mononuclear cells, or monocytes. Whole killed lactobacilli were potent stimulators of IL-12 over a wide range of bacterial concentrations. Lactobacillus paracasei gave the highest levels of IL-12 (1·5 ng/ml in response to 5 × 10 6 bacteria/ml), roughly 10 times more than obtained by stimulation with L. rhamnosus or L. plantarum. Escherichia coli induced on average < 50 pg/ml of IL-12 regardless of the bacterial concentration used. The secretion of free p40 subunit IL-12 followed the same pattern as the secretion of p70 (bioactive IL-12) with regard to the efficiency of different bacteria as stimulators. Escherichia coli was the most efficient trigger of IL-10 production, inducing 0·5 ng/ml IL-10 after stimulation with 5 × 10 6 bacteria/ml. Lactobacillus rhamnosus induced the highest levels of IL-10 among the lactobacilli (0·5 ng/ml) compared with 0·1 ng/ml evoked by L. plantarum or L. paracasei, but 10 times more bacteria were required for optimal stimulation than with E. coli. When neutralizing anti-IL-10 antibodies were added to the cultures, the IL-12-inducing capacity of L. rhamnosus was increased markedly, while that of E. coli remained low. The results show that mucosa-associated lactobacilli can be potent stimulators of IL-12, and thus potentially of cell-mediated immunity, if they pass over the gut epithelial barrier and interact with cells of the gut immune system.

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“…In vitro and in vivo studies have shown that the profile of the cytokine production in an infection is dependent on the causative agent and can even vary with the strain (2,3,41). This is in accordance with the results of the present study.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cytokine Genes during Pneumococcal and NontypeableHaemophilus influenzaeAcute Otitis Media in the Rat

Melhus¹,

Ryan²

2000

Infect Immun

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Acute otitis media (AOM) elicits potent inflammatory responses from the cells of the middle ear mucosa as well as from infiltrating leukocytes. To explore host responses during experimental AOM induced by Streptococcus pneumoniae type 3 and nontypeable Haemophilus influenzae (NTHi), otomicroscopy findings and expression of cytokine genes in the middle ear were monitored up to 1 month postinoculation. The mucosa and infiltrating cells responded rapidly to the bacterial challenge. Otomicroscopically, AOM appeared 1 day after NTHi inoculation and 3 days after pneumococcus inoculation. Pneumococcal AOM was more severe than NTHi otitis, but in general, lower transcript levels were detected in pneumococcus-infected than in NTHi-infected animals. Interleukin-6 (IL-6) mRNA levels peaked at 3 to 6 h for both pneumococcus-infected and NTHiinfected animals. IL-1␣, tumor necrosis factor alpha, and IL-10 mRNA levels peaked at 6 h for NTHi otitis and 1 to 3 days for pneumococcal otitis. Comparing otomicroscopy with expression profiles, it would appear that the majority of cytokine mRNAs had passed their peak before the AOM diagnosis could be made clinically. Only transforming growth factor ␤ mRNA followed a slower time course, peaking very late and continuing expression even after the AOM was otomicroscopically resolved. IL-2 and IL-4 mRNAs were not detected in any animal at any time. Most of the investigated cytokines are very early markers for AOM and may be involved in initiation of inflammation, but they would be poor targets for pharmacological manipulation since their levels decline before clinical signs appear.

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Induction of Phagocyte‐Stimulating Cytokines by In Vitro Stimulation of Human Peripheral Blood Mononuclear Cells with Haemophilus influenzae

Cited by 11 publications

References 26 publications

High cytokine levels in perforated acute otitis media exudates containing live bacteria

High cytokine levels in perforated acute otitis media exudates containing live bacteria

Lactobacilli from human gastrointestinal mucosa are strong stimulators of IL-12 production

Expression of Cytokine Genes during Pneumococcal and NontypeableHaemophilus influenzaeAcute Otitis Media in the Rat

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