Soluble β-(1,3)-glucans enhance LPS-induced response in the monocyte activation test, but inhibit LPS-mediated febrile response in rabbits: Implications for pyrogenicity tests

Eur J Pharm Sci. 2016 Jan 1:81:18-26. doi: 10.1016/j.ejps.2015.09.018. Epub 2015 Sep 30.

Abstract

In the present study, we aimed to determine the influence of β-(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 β-(1,3)-d-glucans elicited the production of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, also known as endogenous pyrogens, but not enough to classify them as pyrogenic according to MAT. The same β-(1,3)-d-glucans samples were non-pyrogenic by RPT. However, β-(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, β-(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 β-(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.

Keywords: Endotoxin; Fever; LPS; Monocyte activation test; Pyrogen; β glucan.

MeSH terms

  • Animals
  • Fever / chemically induced*
  • Fever / immunology
  • Humans
  • Interleukin-1beta / immunology
  • Interleukin-6 / immunology
  • Lipopolysaccharides / pharmacology*
  • Male
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Proteoglycans
  • Pyrogens / pharmacology*
  • Rabbits
  • Tumor Necrosis Factor-alpha / immunology
  • beta-Glucans / pharmacology*

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Proteoglycans
  • Pyrogens
  • Tumor Necrosis Factor-alpha
  • beta-Glucans
  • polysaccharide-K