Local and Systemic Up-regulation of TNFα, IL-1β and IL-6 in Mice Intratracheally Inoculated with Porphyromonas gingivalis

Porphyromonas gingivalis aspiration pneumonia induces local and systemic cytokine responses, but the dynamic of the immune response following lung exposure to live P. gingivalis is poorly understood. Groups of 50 12-week-old male BALB/c mice were inoculated intratracheally with live P. gingivalis ATCC 33277 using low dose (2 x 10(5) colony-forming units [CFU]), high dose (2.9 x 10(9) CFU), or phosphate-buffered saline (PBS; sham-inoculated), and the 3 groups were sacrificed at 2, 6, 24, 72, 168 hours. Lung and serum samples were collected for tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors (sTNFRs), interleukin (IL)-1beta, and IL-6 analysis and lung histology. Pneumonia, only observed in the high-dose group, was associated with an early increase in lung TNF-alpha, IL-1beta, and IL-6, whereas no significant changes were observed in lung sTNFRs. Serum sTNFRs were significantly increased in high-dose animals at all times. IL-1beta elevation occurred earlier in serum than in lungs. IL-1beta was also significantly elevated in serum from low-dose animals at 6 hours. Serum IL-6 and sTNFRs remained raised at 7 days, whereas all other measured cytokines returned to basal levels with resolution of pneumonia. Development of pneumonia is dependent on the P. gingivalis dose; however, part of the cytokine response is unique to the systemic compartment, even in animals that do not develop pneumonia.

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LACK OF SOLUBLE TUMOR NECROSIS FACTOR ALPHA RECEPTOR 1 AND 2 AND INTERLEUKIN-1β COMPARTMENTALIZATION IN LUNGS OF MICE AFTER A SINGLE INTRATRACHEAL INOCULATION WITH LIVEPORPHYROMONAS GINGIVALIS

Nemec

Pavlica

Svete

et al. 2009

Experimental Lung Research

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Aerosolized clindamycin is superior to aerosolized dexamethasone or clindamycin-dexamethasone combination in the treatment of severePorphyromonas gingivalisaspiration pneumonia in an experimental murine model

Nemec

Pavlica

Nemec-Svete

et al. 2011

Experimental Lung Research

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Adjunctive corticosteroid treatment to reduce excessive local inflammatory response in pneumonia is controversial. To study the effects of an early local adjunct dexamethasone treatment on the course of pneumonia and inflammatory/cytokine response, mice were intratracheally inoculated with live Porphyromonas gingivalis and treated with either clindamycin (C), dexamethasone (D), C+D combination, or were not treated (Pg). Six mice from each group were euthanized at 6, 24, 72, and 168 hours after inoculation. Levels of tumor necrosis factor (TNF)-α, soluble TNF-α receptors (sTNFR1 and sTNFR2), interleukin (IL)-1β, and IL-6 in the serum and lung-homogenate supernatant were determined. Lung samples were histopathologically assessed and all findings compared to those found in 24 sham-inoculated mice (phosphate-buffered saline [PBS]). Severe P. gingivalis-induced bronchopneumonia progressed from 24 hours, peaked at 72 hours, and resolved after 168 hours with changes in local and systemic cytokine levels. Clindamycin-treated mice developed only mild bronchopneumonia that resolved fast (72 hours) with an early (6-24 hours) normalization of local and systemic cytokine levels. Similar course of pneumonia and cytokine level changes were observed in mice treated with C+D, but later. Early (6-24 hours) local elevation of sTNFRs was observed in C and C+D groups of mice, whereas nontreated (Pg) mice had increased systemic sTNFRs. Severe bronchopneumonia with delayed resolution was observed in D-group mice, with an early local and systemic decrease in sTNFR1 and persistent elevation of local TNF-α. Clindamycin or a clindamycin-dexamethasone combination treatment significantly improves the course of P. gingivalis-aspiration pneumonia, but more so if clindamycin alone is used. A favorable course of pneumonia seems to be associated with an early elevation of sTNFRs and normalization of TNF-α.

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Local and Systemic Up-regulation of TNFα, IL-1β and IL-6 in Mice Intratracheally Inoculated with Porphyromonas gingivalis

Cited by 2 publications

References 29 publications

LACK OF SOLUBLE TUMOR NECROSIS FACTOR ALPHA RECEPTOR 1 AND 2 AND INTERLEUKIN-1β COMPARTMENTALIZATION IN LUNGS OF MICE AFTER A SINGLE INTRATRACHEAL INOCULATION WITH LIVEPORPHYROMONAS GINGIVALIS

LACK OF SOLUBLE TUMOR NECROSIS FACTOR ALPHA RECEPTOR 1 AND 2 AND INTERLEUKIN-1β COMPARTMENTALIZATION IN LUNGS OF MICE AFTER A SINGLE INTRATRACHEAL INOCULATION WITH LIVEPORPHYROMONAS GINGIVALIS

Aerosolized clindamycin is superior to aerosolized dexamethasone or clindamycin-dexamethasone combination in the treatment of severePorphyromonas gingivalisaspiration pneumonia in an experimental murine model

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