Size dependent induction of proinflammatory cytokines and cytotoxicity of particulate beta-tricalciumphosphate in vitro.

TY - JOUR

T1 - Size dependent induction of proinflammatory cytokines and cytotoxicity of particulate beta-tricalciumphosphate in vitro.

AU - Lange, Tobias

AU - Schilling, Arndt

AU - Peters, Fabian

AU - Mujas, Jan

AU - Wicklein, Daniel

AU - Amling, Michael

PY - 2011

Y1 - 2011

N2 - Cellular responses to particulate calcium phosphate ceramics can lead to inflammatory reactions under certain conditions that depend on particle composition, size and morphology. In this context, the potential influence of varying sizes of particulate beta-tricalciumphosphate (beta-TCP) on the induction of inflammation and cytotoxicity remains to be determined. The present work investigates the effects of beta-TCP particles of five different sizes (1, 3, 13, 32 and 40 ?m) on human peripheral blood mononuclear cells (PBMC) in vitro concerning the release of TNF-alpha, IL-1beta and IL-8 after six and 18 h of incubation (ELISA) as well as intracellular TNF-alpha, IFN-gamma, IL-1alpha, IL-1beta and IL-8 levels within distinct PBMC subpopulations after 12 h (FACS). Potential cytotoxic effects were determined by assaying lactate dehydrogenase (LDH) and morphological analyses (electron microscopy). Beta-TCP 1 ?m did not induce any cytokine after 6 h but slightly increases TNF-alpha, IL-1beta and IL-8 release after 18 h. Larger particles (32 and 40 ?m) consistently caused higher levels of cytokine release by increasing the fraction of cytokine producing monocytes. They also caused higher levels of LDH release as did smaller, phagocytosable particles. These data suggest a less inflammatory and cytotoxic profile of beta-TCP devices with a smaller primary particle size when compared to larger particles.

AB - Cellular responses to particulate calcium phosphate ceramics can lead to inflammatory reactions under certain conditions that depend on particle composition, size and morphology. In this context, the potential influence of varying sizes of particulate beta-tricalciumphosphate (beta-TCP) on the induction of inflammation and cytotoxicity remains to be determined. The present work investigates the effects of beta-TCP particles of five different sizes (1, 3, 13, 32 and 40 ?m) on human peripheral blood mononuclear cells (PBMC) in vitro concerning the release of TNF-alpha, IL-1beta and IL-8 after six and 18 h of incubation (ELISA) as well as intracellular TNF-alpha, IFN-gamma, IL-1alpha, IL-1beta and IL-8 levels within distinct PBMC subpopulations after 12 h (FACS). Potential cytotoxic effects were determined by assaying lactate dehydrogenase (LDH) and morphological analyses (electron microscopy). Beta-TCP 1 ?m did not induce any cytokine after 6 h but slightly increases TNF-alpha, IL-1beta and IL-8 release after 18 h. Larger particles (32 and 40 ?m) consistently caused higher levels of cytokine release by increasing the fraction of cytokine producing monocytes. They also caused higher levels of LDH release as did smaller, phagocytosable particles. These data suggest a less inflammatory and cytotoxic profile of beta-TCP devices with a smaller primary particle size when compared to larger particles.

KW - Humans

KW - Cells, Cultured

KW - Particle Size

KW - Calcium Phosphates/adverse effects

KW - Cytokines/immunology

KW - Inflammation/chemically induced/immunology

KW - L-Lactate Dehydrogenase/analysis

KW - Leukocytes, Mononuclear/drug effects/immunology

KW - Phagocytosis

KW - Humans

KW - Cells, Cultured

KW - Particle Size

KW - Calcium Phosphates/adverse effects

KW - Cytokines/immunology

KW - Inflammation/chemically induced/immunology

KW - L-Lactate Dehydrogenase/analysis

KW - Leukocytes, Mononuclear/drug effects/immunology

KW - Phagocytosis

M3 - SCORING: Journal article

VL - 32

SP - 4067

EP - 4075

JO - BIOMATERIALS

JF - BIOMATERIALS

SN - 0142-9612

IS - 17

M1 - 17

ER -