Modulation of endotoxin- and enterotoxin-induced cytokine release by in vivo treatment with beta-(1,6)-branched beta-(1,3)-glucan.
Leukocytes activated by endotoxin or enterotoxins release proinflammatory cytokines, thereby contributing to the cascade of events leading to septic shock. In the present studies, we analyzed the effects of in vivo administration of a soluble immunomodulator, beta-(1,6)-branched beta-(1,3)-glucan (soluble beta-glucan), on toxin-stimulated cytokine production in monocytes and lymphocytes isolated from treated mice. In vitro stimulation of lymphocytes isolated from soluble beta-glucan-treated mice with lipopolysaccharide (LPS) resulted in enhanced production of interleukin-6 (IL-6) and suppressed production of tumor necrosis factor alpha (TNF-alpha), while stimulation of these cells with staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1) resulted in enhanced production of gamma interferon (IFN-gamma) and suppressed production of IL-2 and TNF-alpha compared to that in cells isolated from untreated mice. In vitro stimulation of monocytes isolated from soluble beta-glucan-treated mice with LPS also resulted in suppressed TNF-alpha production, while stimulation of these cells with SEB or TSST-1 resulted in suppressed IL-6 and TNF-alpha production compared to that in cells isolated from untreated mice. Thus, the overall cytokine pattern of leukocytes from soluble beta-glucan-treated mice reflects suppressed production of proinflammatory cytokines, especially TNF-alpha. Taken together, our results suggest that treatment with soluble beta-glucan can modulate the induction cytokines during sepsis, resulting in an overall decrease in host mortality.
Soltys
J
J
Department of Veterinary Molecular Biology, Montana State University, Bozeman 59717, USA.
Quinn
M T
MT
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001427:Bacterial Toxins; D016207:Cytokines / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology*; D005260:Female; D005936:Glucans / Q000008:administration & dosage*; D007273:Injections, Intramuscular; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology; D047071:beta-Glucans
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D005936:Glucans; D008070:Lipopolysaccharides; D018089:Superantigens; D047071:beta-Glucans; C030107:enterotoxin F, Staphylococcal; C064197:beta-1,6-glucan; C031818:enterotoxin B, staphylococcal; C033363:beta-1,3-glucan