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Eur J Pharm Sci ; 81: 18-26, 2016 Jan 01.
Article in English | MEDLINE | ID: mdl-26428698

ABSTRACT

In the present study, we aimed to determine the influence of ß-(1,3)-d-glucans on the LPS-induced pro-inflammatory cytokine response in the Monocyte Activation Test (MAT) for pyrogens, and on the LPS-induced febrile response in the Rabbit Pyrogen Test (RPT), thus evaluating the resulting effect in the outcome of each test. It was found that ß-(1,3)-d-glucans elicited the production of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α, also known as endogenous pyrogens, but not enough to classify them as pyrogenic according to MAT. The same ß-(1,3)-d-glucans samples were non-pyrogenic by RPT. However, ß-(1,3)-d-glucans significantly enhanced the LPS-induced pro-inflammatory cytokines response in MAT, insomuch that samples containing non-pyrogenic concentrations of LPS become pyrogenic. On the other hand, ß-(1,3)-d-glucans had no effect on sub-pyrogenic LPS doses in the RPT, but surprisingly, inhibited the LPS-induced febrile response of pyrogenic LPS concentrations. Thus, while ß-(1,3)-d-glucans could mask the LPS pyrogenic activity in the RPT, they exerted an overstimulation of pro-inflammatory cytokines in the MAT. Hence, MAT provides higher safety since it evidences an unwanted biological response, which is not completely controlled and is overlooked by the RPT.


Subject(s)
Fever/chemically induced , Lipopolysaccharides/pharmacology , Monocytes/drug effects , Pyrogens/pharmacology , beta-Glucans/pharmacology , Animals , Fever/immunology , Humans , Interleukin-1beta/immunology , Interleukin-6/immunology , Male , Monocytes/immunology , Proteoglycans , Rabbits , Tumor Necrosis Factor-alpha/immunology
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