Aerosolized clindamycin is superior to aerosolized dexamethasone or clindamycin-dexamethasone combination in the treatment of severe Porphyromonas gingivalis aspiration pneumonia in an experimental murine model.

Abstract

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.

• Authors: Ana Nemec, Zlatko Pavlica, Alenka Nemec-Svete, Damijan Eržen, Aleksandra Milutinović, Milan Petelin
• Journal: Experimental lung research (Exp Lung Res) Vol. 38 Issue 1 Pg. 9-18 (Feb 2012) ISSN: 1521-0499 [Electronic] England
• PMID: 22149928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Interleukin-1beta
• Interleukin-6
• Nasal Sprays
• Receptors, Tumor Necrosis Factor, Type I
• Receptors, Tumor Necrosis Factor, Type II
• Tnfrsf1a protein, mouse
• Tumor Necrosis Factor-alpha
• Clindamycin
• Dexamethasone

Topics

• Administration, Inhalation
• Animals
• Anti-Bacterial Agents (administration & dosage)
• Bacteroidaceae Infections (drug therapy, metabolism, microbiology, pathology)
• Bronchopneumonia (drug therapy, metabolism, microbiology, pathology)
• Chemotherapy, Adjuvant (methods)
• Clindamycin (administration & dosage)
• Dexamethasone (administration & dosage)
• Disease Models, Animal
• Interleukin-1beta (blood, metabolism)
• Interleukin-6 (blood, metabolism)
• Lung (drug effects, immunology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Nasal Sprays
• Pneumonia, Aspiration (drug therapy, metabolism, microbiology, pathology)
• Porphyromonas gingivalis (isolation & purification)
• Receptors, Tumor Necrosis Factor, Type I (blood, metabolism)
• Receptors, Tumor Necrosis Factor, Type II (blood, metabolism)
• Tumor Necrosis Factor-alpha (blood, metabolism)