Anti-CD14 monoclonal antibodies inhibit the production of tumor necrosis factor alpha and interleukin-10 by human monocytes stimulated with killed and live Haemophilus influenzae or Streptococcus pneumoniae organisms

In previous studies, we have shown that intact, heat-killed, gram-negative bacteria (GNB) and gram-positive bacteria (GPB) can stimulate the productio n of various proinflammatory and anti-inflammatory cytokines. The objective of the present study was to investigate whether the production of tumor ne crosis factor alpha (TNF) and interleukin-10 (IL-10) by human monocytes sti mulated by intact heat-killed or live Haemophilus influenzae or Streptococc us pneumoniae is mediated by CD14, Two anti-CD14 monoclonal antibodies (MAb s)were used to study the interaction between human monocytes and bacteria; lipopolysaccharide (LPS) was used to validate the effect of anti-CD14 MAb, MAb 18E12 decreased significantly TNF and IL-10 production upon stimulation with LPS or heat-killed bacteria and TNF production during stimulation by live bacteria. MAb My-4 decreased production of TNF and IL-10 by monocytes stimulated with LPS, IL-10 but not TNF production upon stimulation with hea t-killed H, influenzae, and production of neither TNF nor IL-10 upon stimul ation with S, pneumoniae, Together, these results led to the conclusion tha t CD14 is involved in the recognition and stimulation of human monocytes by intact GNB and GPB. Consequentially, the option for adjunctive treatment o f severe infections with anti-CD14 MAb is postulated.