ASSESSMENT OF THE EFFECT OF CANDIDATE ANTIINFLAMMATORY TREATMENTS ON THE INTERACTION BETWEEN MENINGOCOCCI AND INFLAMMATORY CELLS IN-VITRO IN A WHOLE-BLOOD MODEL
B. Chan et al., ASSESSMENT OF THE EFFECT OF CANDIDATE ANTIINFLAMMATORY TREATMENTS ON THE INTERACTION BETWEEN MENINGOCOCCI AND INFLAMMATORY CELLS IN-VITRO IN A WHOLE-BLOOD MODEL, Biotherapy, 9(4), 1996, pp. 221-228
A wide range of immunomodulating agents are now available which may be
of benefit in reducing inflammatory cell activation in meningococcal
sepsis. In order to facilitate selection of candidate anti-inflammator
y agents for clinical trials, we have used an in vitro whole blood mod
el to evaluate the effects on meningococcal induced neutrophil and mon
ocyte activation, of dexamethasone, prostacyclin, pentoxifylline and a
human IgM anti-lipid A monoclonal antibody (HA-1A). Known concentrati
ons of heat and penicillin killed meningococci were added to whole blo
od and the time course of cellular activation was determined. Using el
astase-alpha(1)-antitrypsin (elastase-alpha(1)-AT) and TNF alpha produ
ction as markers of neutrophil and monocyte activation respectively, p
lasma levels of elastase-alpha(1)-AT and TNF alpha were found to incre
ase in a dose-dependant manner. Elastase-alpha(1)-AT was detected earl
y, with most release occurring between 15-30 min whereas TNF alpha was
detected later, between 120-180 min. Dexamethasone, prostacyclin and
pentoxifylline caused a dose dependant inhibition of TNF alpha release
but had no effect on elastase release. HA-1A had no effect on either
TNF alpha or elastase release. This model may be useful in determining
the sequence of inflammatory cell activation and in selecting candida
te anti-inflammatory agents for evaluation in clinical trials.