Pretreatment of Mice with Clindamycin Improves Survival of Endotoxic Shock by Modulating the Release of Inflammatory Cytokines

Hirata, Norio; Hiramatsu, Kazufumi; Kishi, Kenji; Yamasaki, Takahiro; Ichimiya, Tomoku; Nasu, Masaru

doi:10.1128/aac.45.9.2638-2642.2001

Cited by 38 publications

(24 citation statements)

References 19 publications

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“…Effective management of these infections includes early and appropriate antimicrobial treatment, which could also impact the production of virulent toxins. Antibiotics are known to modulate immune functions during inflammation or serious infections (29), and different classes of antimicrobials have various effects (32). Antibiotics that inhibit protein synthesis may reduce toxin production while potent cell wall inhibitors stimulate an increase in toxin release; however, these observations in vitro are limited to subinhibitory concentrations (21,53).…”

Section: Discussionmentioning

confidence: 93%

Simulated Antibiotic Exposures in an In Vitro Hollow-Fiber Infection Model Influence Toxin Gene Expression and Production in Community-Associated Methicillin-Resistant Staphylococcus aureus Strain MW2

Pichereau

Pantrangi

Couet

et al. 2012

Antimicrob Agents Chemother

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Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain MW2 harbors a plethora of toxins to mediate its virulence. However, toxin expression and regulation with simulated clinical antimicrobial exposures are unclear. This study evaluated these relationships using an in vitro pharmacodynamic hollow-fiber infection model. Clinical doses of clindamycin, linezolid, minocycline, trimethoprim-sulfamethoxazole (SXT), and vancomycin were simulated over 72 h against MW2 in the hollow fiber model. Expression levels of lukSF-PV and enterotoxin genes sec4, sek, seq, and sel2 were quantified by realtime PCR. Panton-Valentine leukocidin (PVL) was quantified by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was determined on polymorphonuclear cells (PMNs). Vancomycin produced the maximum MW2 killing (2.53 log 10 CFU/ml) after the first dose, but the greatest sustained killing over 72 h occurred with linezolid and clindamycin. Vancomycin and minocycline induced gene upregulation from 0 to 8 h, followed by downregulation for the remaining simulation period. Clindamycin decreased gene expression in the first 24 h, followed by moderate increases (2.5-fold) thereafter. Linezolid increased gene expression 11.4-to 200.4-fold but inhibited PVL production (0.6 ؎ 0.3 versus 5.9 ؎ 0.2 g/ml, linezolid versus control at 72 h; P < 0.05).

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Section: Discussionmentioning

confidence: 93%

Simulated Antibiotic Exposures in an In Vitro Hollow-Fiber Infection Model Influence Toxin Gene Expression and Production in Community-Associated Methicillin-Resistant Staphylococcus aureus Strain MW2

Pichereau

Pantrangi

Couet

et al. 2012

Antimicrob Agents Chemother

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“…Furthermore, these anticytokine effects on inflammatory cytokines have been studied at a molecular level (12,14,16). It was recently reported that clindamycin (CLI) reduces tumor necrosis factor alpha (TNF-␣) concentrations in lipopolysaccharide (LPS)-stimulated THP-1 cells (8) and that CLI decreases TNF-␣ and interleukin 1␤ (IL-1␤) concentrations and increases serum IL-6 concentrations, as well as reducing mortality in the mouse model (4). The present study showed the mechanism of modulation by CLI of inflammatory-cytokine production by LPS-stimulated macrophages, both in vitro and in vivo.…”

mentioning

confidence: 99%

Clindamycin Modulates Inflammatory-Cytokine Induction in Lipopolysaccharide-Stimulated Mouse Peritoneal Macrophages

Nakano

Hiramatsu

Kishi

et al. 2003

Antimicrob Agents Chemother

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We investigated the mechanism by which clindamycin (CLI) modulates cytokine induction after lipopolysaccharide (LPS) stimulation. Although CLI decreased the intracellular expression levels of tumor necrosis factor alpha and interleukin 1␤ (IL-1␤) and increased IL-6 expression in macrophages, cytokine mRNA expression levels were similar in CLI-treated and untreated groups. Our findings suggest that CLI modulates cytokine production in LPS-stimulated macrophages.Anticytokine effects, which are independent of their antibacterial properties, have been reported elsewhere for several antimicrobial agents (2, 7, 9). Furthermore, these anticytokine effects on inflammatory cytokines have been studied at a molecular level (12,14,16). It was recently reported that clindamycin (CLI) reduces tumor necrosis factor alpha (TNF-␣) concentrations in lipopolysaccharide (LPS)-stimulated THP-1 cells (8) and that CLI decreases TNF-␣ and interleukin 1␤ (IL-1␤) concentrations and increases serum IL-6 concentrations, as well as reducing mortality in the mouse model (4). The present study showed the mechanism of modulation by CLI of inflammatory-cytokine production by LPS-stimulated macrophages, both in vitro and in vivo.Two milliliters of 4% thioglycolate fluid medium (Difco, Detroit, Mich.) was intraperitoneally injected into 10-week-old C3H/HeN male mice. After 4 days peritoneal lavage fluid was collected and cultured on plastic plates in Iscove's modified Dulbecco's medium supplemented with 10% heat-inactivated fetal bovine serum at 37°C under 5% CO 2 for 90 min. Adherent cells were used as the macrophages (esterase staining confirmed that 95%

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“…[29][30][31] Taken together with the culture results, sustained delivery of clindamycin in infected defects both prevents progression to frank infection and restores or maintains the inflammatory cytokine profile seen in noninfected induced membranes. The continued inflammatory state seen in the +Inc/-Abx group is not a favorable state for the bone regeneration.…”

Section: Discussionmentioning

confidence: 99%

Effects of Local Antibiotic Delivery from Porous Space Maintainers on Infection Clearance and Induction of an Osteogenic Membrane in an Infected Bone Defect

Shah

Smith

Tatara

et al. 2017

Tissue Engineering Part A

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Reconstruction of large bone defects can be complicated by the presence of both infection and local antibiotic administration. This can be addressed through a two-stage reconstructive approach, called the Masquelet technique, that involves the generation of an induced osteogenic membrane over a temporary poly(methyl methacrylate) (PMMA) space maintainer, followed by definitive reconstruction after the induced membrane is formed. Given that infection and antibiotic delivery each have independent effects on local tissue response, the objective of this study is to evaluate the interaction between local clindamycin release and bacterial contamination with regards to infection prevention and the restoration of pro-osteogenic gene expression in the induced membrane. Porous PMMA space maintainers with or without clindamycin were implanted in an 8 mm rat femoral defect model with or without Staphylococcus aureus inoculation for 28 days in a full-factorial study design (four groups, n = 8/group). Culture results demonstrated that 8/8 animals in the inoculated/no antibiotic group were infected at 4 weeks, which was significantly reduced to 1/8 animals in the inoculated/antibiotic group. Quantitative polymerase chain reaction analysis demonstrated that clindamycin treatment restores inflammatory cytokine and growth factor expression to the same levels as the no inoculation/no antibiotic group, demonstrating that clindamycin can ameliorate the negative effects of bacterial inoculation and does not itself negatively impact the expression of important cytokines. Main effect analysis shows that bacterial inoculation and clindamycin treatment have independent and interacting effects on the gene expression profile of the induced membrane, further highlighting that antibiotics play an important role in the regeneration of infected defects apart from their antimicrobial properties.

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Pretreatment of Mice with Clindamycin Improves Survival of Endotoxic Shock by Modulating the Release of Inflammatory Cytokines

Cited by 38 publications

References 19 publications

Simulated Antibiotic Exposures in an In Vitro Hollow-Fiber Infection Model Influence Toxin Gene Expression and Production in Community-Associated Methicillin-Resistant Staphylococcus aureus Strain MW2

Simulated Antibiotic Exposures in an In Vitro Hollow-Fiber Infection Model Influence Toxin Gene Expression and Production in Community-Associated Methicillin-Resistant Staphylococcus aureus Strain MW2

Clindamycin Modulates Inflammatory-Cytokine Induction in Lipopolysaccharide-Stimulated Mouse Peritoneal Macrophages

Effects of Local Antibiotic Delivery from Porous Space Maintainers on Infection Clearance and Induction of an Osteogenic Membrane in an Infected Bone Defect

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