Cytokine production in an ex vivo whole blood model following induction by group B streptococcal polysaccharides and lipoteichoic acid.

Abstract

An excessive release of pro-inflammatory cytokines, such as TNF-α and IL-1, during bacterial invasive infections can mediate several pathophysiologic phenomena2, 9, 11. Group B streptococci (GBS) are important causes of neonatal sepsis and invasive infections in adults, which are often rapidly fatal despite appropriate therapy. High TNF-α and IL-6 plasma levels were found in children with GBS sepsis2. Infection with GBS can induce the production of TNF-α, IL-1, IL-6 and interferon γ in neonatal rats10. Moreover, in these animals, by the use of heat-killed isogenic GBS mutant strains devoid of the capsular type-specific polysaccharide it was shown that this polysaccharide would not be the only factor which elicits the release of TNF-α6. Many of the host responses to gram-negative bacteria could be attributed to lipopolysaccharide (LPS), which triggers monocytes to release inflammatory cytokines5. Recent studies indicated that, aside from LPS, peptidoglycan and various polysaccharides, including uronic acid, polyuronic acid, rhamnose-glucose polymers, trigger monocytes to release cytokines1, 7, 8. This led us to investigate whether TNF-α, IL-1β, IL-6 and IL-8 could be induced in human whole blood by the addition of purified surface components of GBS, namely group (CHO-B), type Ia (CHO-Ia) and III (CHO-III) specific polysaccharides or lipoteichoic acid (LTA).