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Effect of Aluminum on $TNF-{\alpha}$ Secretion from Murine RAW264.7 Cells for Endotoxin Detection in Hepatitis B Vaccines  

Park Chul-Yong (College of Pharmacy, Sungkyunkwan University)
Lee Sun-Suk (College of Pharmacy, Sungkyunkwan University)
Rhee Dong-Kwon (College of Pharmacy, Sungkyunkwan University)
Publication Information
Journal of Microbiology and Biotechnology / v.16, no.2, 2006 , pp. 219-225 More about this Journal
Abstract
The rabbit pyrogen test and Limulus amoebocyte lysate (LAL) assay have been used to detect endotoxins present in vaccines. Currently, the rabbit pyrogen test is used to detect endotoxins in hepatitis B (HB) vaccines, even though the HB surface protein, which is the active ingredient, is overexpressed in and purified from eukaryotic cells that lack these endotoxins. Although the LAL clot assay is sensitive and reliable and can be used to replace the rabbit pyrogen test, its reaction is limited by the lack of responsiveness to the Gram-positive bacterial components. Furthermore, aluminum hydroxide in the HB vaccine can interfere with the LAL assay. In contrast, macrophages can detect the endotoxin as well as other pyrogens, and secrete $TNF-{\alpha}$. Therefore, this study was undertaken to examine the possibility of replacing the animal tests with a more efficient $TNF-{\alpha}$ secretion assay. With this in mind, we determined if aluminum hydroxide in the HB vaccines affects the $TNF-{\alpha}$ secretion assay. HB vaccines and the HB protein solutions spiked with lipopolysaccharide (LPS) produced the same level of dose-dependent $TNF{\alpha}$ secretion and temperature increase in rabbits, indicating that aluminum hydroxide in the HB vaccine does not interfere with the pyrogenic response in rabbits, nor does it interfere with $TNF-{\alpha}$ secretion. In addition, the $TNF-{\alpha}$ assay was found to be more sensitive than the LAL assay, and correlated well with the pyrogen test and the LAL assay. These results suggest that the $TNF-{\alpha}$ assay in RAW264.7 cells is a good substitute for the current pyrogen assays that are used for detecting LPS in HB vaccines as well as in other vaccines containing aluminum.
Keywords
LAL clot assay; hepatitis; vaccine; endotoxin; $TNF-{\alpha}$; pyrogen;
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1 Chung, T. W., U. H. Jin, and C. H. Kim. 2003. Salmonella typhimurium LPS confers its resistance to antibacterial agents of baicalin of Scutellaria baicalensis George and novobiocin: Complementation of the rfaE gene required for ADP-L-glycero-D-manno-heptose biosynthesis of lipopolysaccharide. J. Microbiol. Biotechnol. 13: 564-570
2 Eperon, S. and T. W. Jungi. 1997. Human monocytoid cell lines as indicators of endotoxin: Comparison with rabbit pyrogen and Limulus amoebocyte lysate assay. J. Immunol. Methods 207: 135-145   DOI   ScienceOn
3 Palsson-McDermott, E. M. and L. A. O'Neill. 2004. Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. Immunology 113: 153-162   DOI   ScienceOn
4 Prehn, J. L., D. L. Fagan, S. C. Jordan, and J. S. Adams. 1992. Potentiation of lipopolysaccharide-induced tumor necrosis factor-alpha expression by 1,25-dihydroxyvitamin D3. Blood 80: 2811-2816
5 Shany, S., R. Levy, and C. Chaimovitz. 1995. Of 1,25- dihydroxyvitamin D on the immune activity of peritoneal macrophages in continuous ambulatory peritoneal dialysis patients. Nephron 69: 367-370   DOI
6 Ding, J. L. and B. Ho. 2001. A new era in pyrogen testing. Trends Biotechnol. 19: 277-281   DOI   ScienceOn
7 Rigby, W. F., S. Denome, and M. W. Fanger. 1987. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3: Specific inhibition at the level of messenger RNA. J Clin. Invest. 79: 1659- 1664   DOI
8 Bae, C. S., G. Y. Lim, J. S. Kim, and B. K. Hur. 2003. Quadrivalent combined vaccine, including diphtheria toxoid, tetanus toxoid, detoxified whole cell pertussis, and hepatitis B surface antigen. J. Microbiol. Biotechnol. 13: 338-343
9 Bhalla, A. K., E. P. Amento, and S. M. Krane. 1986. Differential effects of 1,25-dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophages: Inhibition of interleukin-2 and augmentation of interleukin-1 production. Cell. Immunol. 98: 311-322   DOI   ScienceOn
10 Campbell, A., E. Y. Yang, M. Tsai-Turton, and S. C. Bondy. 2002. Pro-inflammatory effects of aluminum in human glioblastoma cells. Brain Res. 933: 60-65   DOI   ScienceOn
11 Cadenas, S. and A. M. Cadenas. 2002. Fighting the stranger-antioxidant protection against endotoxin toxicity. Toxicology 180: 45-63   DOI   ScienceOn
12 Cosnes, A., M. L. Flechet, and J. Revuz. 1990. Inflammatory nodular reactions after hepatitis B vaccination due to aluminium sensitization. Contact Dermatitis 23: 65-67   DOI   ScienceOn
13 Binderup, L. 1992. Immunological properties of vitamin D analogues and metabolites. Biochem. Pharmacol. 43: 1885- 1892   DOI   ScienceOn
14 Jungi, T. W. 1990. A turbidimetric assay in an ELISA reader for the determination of mononuclear phagocyte procoagulant activity. J. Immunol. Methods 133: 21-29   DOI   ScienceOn
15 Beutler, B., J. Mahoney, N. Le Trang, P. Pekala, and A. Cerami. 1985. Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J. Exp. Med. 161: 984-995   DOI
16 Riancho, J. A., M. T. Zarrabeitia, A. L. de Francisco, J. A. Amado, J. Napal, M. Arias, and J. Gonzalez-Macias. 1993. Vitamin D therapy modulates cytokine secretion in patients with renal failure. Nephron 65: 364-368   DOI
17 Panichi, V., S. D. Pietro, B. Andreini, A. M. Bianchi, M. Migliori, D. Taccola, L. Giovannini, C. Tetta, and R. Palla. 1998. Calcitriol modulates in vivo and in vitro cytokine production: A role for intracellular calcium. Kidney Int. 54: 1463-1469   DOI   ScienceOn
18 Park, C. Y., S. H. Jung, J. P. Bak, S. S. Lee, and D. K. Rhee. 2005. Comparison of the rabbit pyrogen test and Limulus amoebocyte lysate (LAL) assay for endotoxin in hepatitis B vaccines and the effect of aluminum hydroxide. Biologicals [in press]
19 Poole, S., R. Thorpe, A. Meager, and A. J. Gearing. 1988. Assay of pyrogenic contamination in pharmaceuticals by cytokine release from monocytes. Dev. Biol. Stand. 69: 121- 123
20 Weary, M. E. 1989. Understanding and setting endotoxin limits. J. Parenteral Sci. Technol. 44: 110-111
21 Hansen, E. W. and J. D. Christensen. 1990. Comparison of cultured human mononuclear cells, Limulus amebocyte lysate and rabbits in the detection of pyrogens. J. Clin. Pharm. Ther. 15: 425-433
22 Yamamoto, A., M. Ochiai, M. Kataoka, H. Toyoizumi, and Y. Horiuchi. 2002. Development of a highly sensitive in vitro assay method for biological activity of endotoxin contamination in biological products. Biologicals 30: 85- 92   DOI   ScienceOn
23 Ray, A., K. Redhead, S. Selkirk, and S. Poole. 1991. Variability in LPS composition, antigenicity and reactogenicity of phase variants of Bordetella pertussis. FEMS Microbiol. Lett. 63: 211-227   DOI
24 Cohen, M. L., A. Douvdevani, C. Chaimovitz, and S. Shany. 2001. Regulation of TNF-alpha by 1alpha,25-dihydroxyvitamin D3 in human macrophages from CAPD patients. Kidney Int. 59: 69-75   DOI   ScienceOn
25 Furman, I., C. Baudet, and P. Brachet. 1996. Differential expression of M-CSF, LIF, and TNF-alpha genes in normal and malignant rat glial cells: Regulation by lipopolysaccharide and vitamin D. J. Neurosci Res. 46: 360-366   DOI   ScienceOn
26 Laude-Sharp, M., N. Haeffner-Cavaillon, M. Caroff, F. Lantreibecq, C. Pusineri, and M. D. Kazatchkine. 1990. Dissociation between the interleukin 1-inducing capacity and Limulus reactivity of lipopolysaccharides from gram-negative bacteria. Cytokine 2: 253-258   DOI   ScienceOn
27 Levin, J. and F. B. Bang. 1964. A description of cellular coagulation in the Limulus. Bull. Johns Hopkins Hosp. 155: 337-345
28 Demircan, M., O. Ergun, C. Coker, F. Yilmaz, S. Avanoglu, and G. Ozok. 1998. Aluminum in total parenteral nutrition solutions produces portal inflammation in rats. J. Pediatr. Gastroenterol. Nutr. 26: 274-278   DOI   ScienceOn
29 Fagan, D. L., J. L. Prehn, J. S. Adams, and S. C. Jordan. 1991. The human myelomonocytic cell line U-937 as a model for studying alterations in steroid-induced monokine gene expression: Marked enhancement of lipopolysaccharide-stimulated interleukin-1 beta messenger RNA levels by 1,25-dihydroxyvitamin D3. Mol. Endocrinol. 5: 179-186   DOI   ScienceOn
30 Nakagawa, Y., H. Maeda, and T. Murai. 2002. Evaluation of the in vitro pyrogen test system based on proinflammatory cytokine release from human monocytes: Comparison with a human whole blood culture test system and with the rabbit pyrogen test. Clin. Diagn. Lab. Immunol. 9: 588-597   DOI
31 Werner-Felmayer, G., G. Baier-Bitterlich, D. Fuchs, A. Hausen, C. Murr, G. Reibnegger, E. R. Werner, and H. Wachter. 1995. Detection of bacterial pyrogens on the basis of their effects on gamma interferon-mediated formation of neopterin or nitrite in cultured monocyte cell lines. Clin. Diagn. Lab. Immunol. 2: 307-313