In vitro inhibition of group B streptococcus-induced polymorphonuclear leukocyte aggregation

Evidence suggests that part of the pathophysiologic response seen in group B streptococcal (GBS) sepsis may be due to polymorphonuclear leukocyte (PMN) activation. Indomethacin (INDO), which inhibits eicosanoid metabolism, attenuates the pathophysiologic response stimulated by GBS, possibly due to inhibition of PMN aggregation. We examined the capability of two eicosanoid metabolism inhibitors, INDO and nordihydroguaiaretic acid (NDGA), to inhibit PMN aggregation induced by heat-inactivated opsonized GBS and GBS-activated plasma. Opsonized GBS-induced PMN aggregation was inhibited by INDO (50–500μM) and NDGA (1–100μM). Over similar concentration ranges, INDO and NDGA had no significant eifect on PMN aggregation induced by GBS-activated plasma. PMNs in plasma aggregate in response to unopsonized GBS. The stimuli for aggregation are opsonized GBS and GBS-activated plasma. INDO (50–500μM) was unable to inhibit aggregation under this condition. Over the same concentration range in which INDO inhibited opsonized GBS-induced PMN aggregation, INDO was unable to inhibit opsonized GBS-induced superoxide production in PMNs. NDGA was examined but was found to interfere with the assay. The above evidence suggests PMN aggregation via eicosanoid metabolism may play a role in GBS-induced sepsis, which may be attenuated by agents such as INDO and NDGA.