The mechanism of action of a single dose of methylprednisolone on acute inflammation in vivo.
A model system for the study of inflammation in vivo has been developed using the 16-h polyvinyl sponge implant in the rat. This system allows for simultaneous measurement of in vivo chemotaxis, volume of fluid influx, and fluid concentrations of lysosomal and lactic dehydrogenase (LDH) enzymes. In addition, the enzyme content of inflammatory fluid neutrophils may also be determined. A parallel time course of neutrophil and lysosomal enzyme influx into sponge implants was observed. This was characterized by an initial lag phase and a rapid increase between 5 and 16 h. The origin of supernatant LDH and lysosomal enzymes was studied with anti-neutrophil serum to produce agranulocytic rats. Inflammatory fluid in these rats was almost acellular and contained decreased concentrations of beta glucuronidase (-96%) and LDH (-74%). In control rats all of the supernatant beta glucuronidase could be accounted for by cell death and lysis, as estimated from measurements of soluble DNA. Only 15-20% of the LDH activity could be accounted for on the basis of cell lysis. The remainder was derived from neutrophil-mediated injury to connective tissue cells. Large intravascular doses of methylprednisolone markedly inhibited neutrophil influx into sponges and adjacent connective tissue. Secondary to decreased neutrophil influx, fewer neutrophils were available for lysis, and lysosomal enzyme levels in inflammatory fluid decreased. No evidence for intracellular or extracellular stabilization of neutrophil lysosomal granules by methylprenisolone was found.
D000818:Animals; D002633:Chemotaxis / Q000187:drug effects; D005110:Extracellular Space / Q000201:enzymology / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D011145:Polyvinyls; D051381:Rats; D013997:Time Factors
D011145:Polyvinyls; D008775:Methylprednisolone