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 phenomena^{2, 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 cytokines^{1, 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).