RECENT STUDIES HAVE DEMONSTRATED THAT IT IS POSSIBLE TO PREVENT AND TREAT GRAM NEGATIVE SHOCK WITH ANTISERUM TO ROUGH STRAINS OF GRAM NEGATIVE BACTERIA, YET THERE IS NO PREDICTIVE IN VITRO TEST OF ANTISERUM EFFICACY.

RECENT STUDIES HAVE DEMONSTRATED THAT IT IS POSSIBLE TO PREVENT AND TREAT GRAM NEGATIVE SHOCK WITH ANTISERUM TO ROUGH STRAINS OF GRAM NEGATIVE BACTERIA, YET THERE IS NO PREDICTIVE IN VITRO TEST OF ANTISERUM EFFICACY. WE HAVE DEVELOPED AN IN VITRO ASSAY OF THE ABILITY OF SERUM TO NEUTRALIZE THE BIOLOGICAL ACTIVITY OF ENDOTOXIN USING THE LIMULUS AMEBOCYTE LYSATE (LAL) TEST. THIS STUDY WILL: (1) REFINE THE IN VITRO ASSAY BY RE-EXAMINATION OF THE REACTION PARAMETERS, (2) EVALUATE THE IN VITRO ASSAY IN A PILOT EXPERIMENT TESTING THE SERA OF SEVERAL PATIENT GROUPS FOR ENDOTOXIN NEUTRALIZING CAPACITY, AND (3) TEST THE ABILITY OF THE IN VITRO ASSAY TO PREDICT THE THERAPEUTIC EFFICACY OF SELECTED SERA IN THE PREVENTION OF ENDOTOXIN RESPONSE IN AN ANIMAL MODEL. WE HOPE THAT THE IN VITRO ASSAY WILL HAVE DIAGNOSTIC APPLICATIONS FOR PREDICTING A PATIENT'S SUSCEPTIBILITY TO GRAM NEGATIVE SHOCK. WE ALSO HOPE THAT THE IN VITRO ASSAY WILL BE USEFUL IN THE ELUCIDATION OF THE MECHANISMS RESPONSIBLE FOR PROTECTION AGAINST ENDOTOXIN AND IN THE DEVELOPMENT OF A THERAPEUTIC AGENT FOR ADMINISTRATION TO PATIENTS IN GRAM NEGATIVE SHOCK.THIS PROPOSAL IS SUBMITTED TO THE NATIONAL INSTITUTES OF ALLERGY AND INFECTIOUS DISEASE RESEARCH PROGRAM.