BIOCHEMICAL MEDIATORS OF MENINGEAL INFLAMMATORY RESPONSE TO GROUP-B STREPTOCOCCUS IN THE NEWBORN PIGLET MODEL

The meningeal inflammatory response to a heat-killed mutant unencapsul ated strain of type III group B Streptococcus (GBS) was studied in a n ewborn piglet model. GBS (10(9) colony-forming unit equivalents) or sa line (control) was inoculated intraventricularly. Serial cerebrospinal fluid measurements were done at baseline and over the course of the n ext 24 h for cytochemical changes and production of tumor necrosis fac tor (TNF) and prostaglandins. In separate experiments, we defined the time course of early changes during the first 6 h and dose response re lationship over a range of inocula 10(6) to 10(9) colony-forming unit equivalents. The intraventricular inoculation of the heat-killed unenc apsulated GBS induced marked leukocytosis and increased protein by 6 h . These changes were preceded by a several hundredfold increase in TNF (maximum at 2 h) and prostaglandins (maximum at 2-4 h). The early and sharp rise in TNF suggests its pivotal role in initiating the inflamm atory cascade. The magnitude of the inflammatory response increased wi th increasing bacterial dose over the range studied. To study the effe ct of encapsulation of GBS in the induction of meningeal inflammation, we compared the response to the unencapsulated mutant strain with tha t to the encapsulated parent strain. The encapsulated strain produced much smaller inflammatory changes, and only with high doses of bacteri a. The GBS cell wall appeared to be the primary bacterial product trig gering inflammation. Intraventricular injection of the heat-killed une ncapsulated GBS with exposed cell wall can serve as a valid model for studying neonatal meningitis.