title: 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.
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.
authors.affiliation: Biochemistry Department, Center for Pharmaceutical Research and Development, Ave. 26 No. 1605 e/ Ave. 51 y Boyeros, Plaza, CP 10600 Havana, Cuba.
authors.forename: Zenia
authors.initials: Z
authors.lastname: Pardo-Ruiz
authors.affiliation: Biological Control Laboratory, Center for Pharmaceutical Research and Development, 17 St. No. 6208 e/ 62 y 64, Playa, CP 11300 Havana, Cuba.
authors.forename: Dalia E
authors.initials: DE
authors.lastname: Menéndez-Sardiñas
authors.affiliation: Biochemistry Department, Center for Pharmaceutical Research and Development, Ave. 26 No. 1605 e/ Ave. 51 y Boyeros, Plaza, CP 10600 Havana, Cuba.
authors.forename: Anabel
authors.initials: A
authors.lastname: Pacios-Michelena
authors.affiliation: Biological Control Laboratory, Center for Pharmaceutical Research and Development, 17 St. No. 6208 e/ 62 y 64, Playa, CP 11300 Havana, Cuba.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gabilondo-Ramírez
authors.affiliation: Biochemistry Department, Center for Pharmaceutical Research and Development, Ave. 26 No. 1605 e/ Ave. 51 y Boyeros, Plaza, CP 10600 Havana, Cuba.
authors.forename: Vivian
authors.initials: V
authors.lastname: Montero-Alejo
authors.affiliation: Biochemistry Department, Center for Pharmaceutical Research and Development, Ave. 26 No. 1605 e/ Ave. 51 y Boyeros, Plaza, CP 10600 Havana, Cuba. Electronic address: rolando.perdomo@infomed.sld.cu.
authors.forename: Rolando
authors.initials: R
authors.lastname: Perdomo-Morales
mesh_terms: D000818:Animals; D005334:Fever / Q000139:chemically induced* / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011509:Proteoglycans; D011749:Pyrogens / Q000494:pharmacology*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D047071:beta-Glucans / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011509:Proteoglycans; D011749:Pyrogens; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; C010770:polysaccharide-K
keywords: Endotoxin; Fever; LPS; Monocyte activation test; Pyrogen; β glucan