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

Abstract

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%

In vivo and in vitro effects of fluoroquinolones on lipopolysaccharide-induced pro-inflammatory cytokine production

“…Some of them have been reported to have an activity to modify biological responses. For example, 14-membered macrolides 1-3 and clindamycin 4 have been reported to modify infl ammatory responses. And amphotericin B, a polyene macrolide, has been reported to augment tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages.…”

Tigecycline has no effect on cytokine release in an ex vivo endotoxin model of human whole blood

“…fluoroquinolones, oxazolidinones (linezolid), clindamycin, fosfomycin and tetracyclines, are able to modulate the cytokine response in experimental endotoxaemia [2][3][4][5][6][7][8]. Among others, antibiotics of the tetracycline family were found to protect mice against lethal doses of lipopolysaccharide (LPS).…”

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

“…[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.…”