Chemical and biological evaluation of endotoxin contamination on natural rubber latex products.
Relationship between pyrogenicity and bacterial endotoxin contamination on latex products was demonstrated by chemical analysis and biological assays. In commercially available latex products' surveillance, water extracts prepared from one surgical glove and two silicone elastomer-coated Foley catheters sterilized by gamma-irradiation were obviously pyrogenic in rabbits. The induced fever was monophasic at low dose of the pyrogenic extracts and biphasic at high dose. These extracts exhibited limulus amebocyte lysate gelation activity, and induced inflammatory cytokine (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) production from MM6-CA8 human monocytoid cells. These biological properties, including pyrogenicity, completely disappeared by treating the pyrogenic extracts with endotoxin-adsorbent affinity column. Limulus amebocyte lysate activity and cytokine production from MM6-CA8 cells induced by the extracts were significantly decreased by endotoxin inhibitors, an active fragment peptide of an 18-kDa cationic antimicrobial protein and a synthetic lipid A B464 analogue. Furthermore, very small amounts of 2-keto-3-deoxyoctonate and 3-hydroxy fatty acid, which are common constituents of bacterial endotoxins, were detected by gas chromatography-mass spectrometry analysis of the pyrogenic extracts. These findings clearly showed that the pyrogenicity found in these latex products originated from endotoxins contaminating the products.
Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. haishima@nihs.go.jp
Y
Y
Haishima
T
T
Murai
Y
Y
Nakagawa
M
M
Hirata
T
T
Yagami
A
A
Nakamura
D000818:Animals; D001672:Biocompatible Materials / Q000032:analysis; D001681:Biological Assay; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004340:Drug Contamination; D004731:Endotoxins / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000032:analysis; D008422:Materials Testing; D011749:Pyrogens / Q000032:analysis; D011817:Rabbits; D012408:Rubber / Q000032:analysis*
D001672:Biocompatible Materials; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D011749:Pyrogens; D012408:Rubber