期刊
TOXICOLOGIC PATHOLOGY
卷 48, 期 7, 页码 845-856出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0192623320957281
关键词
acute phase proteins; fibrinogen; vaccine; adjuvant; rat; α -2 macroglobulin; α -1 acid glycoprotein
The objectives were to characterize the kinetics of acute phase proteins (APPs) alpha-2 macroglobulin (A2M), alpha-1 acid glycoprotein (A1AGP), and fibrinogen (FIB), and injection site macroscopic and microscopic findings following intramuscular administration of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (TDaP; Adacel); adjuvants (aluminum phosphate [AlPO4]; aluminum hydroxide, Al[OH](3); CpG/Al[OH](3); or Quillaja saponaria 21 [QS-21]); or saline to female Wistar Han rats. Intravascular lipopolysaccharide (LPS) was a positive control. Injection sites and lymph nodes were evaluated microscopically, using hematoxylin and eosin (H&E) stained sections, 48 hours postdose (HPD) and compared with APP concentrations; A2M and A1AGP were measured using Meso Scale Discovery analyzer. Fibrinogen was measured on STA Compact analyzer. In a time-course study, APP peaked at 24 or 48 HPD. In a subsequent study at 48 HPD, injection site microscopic changes included inflammation and muscle degeneration/necrosis, which was different in severity/nature between groups. The APPs were not increased in rats administered saline, Al(OH)(3), or AlPO4. Fibrinogen and A1AGP increased in rats administered CpG/Al(OH)(3), QS-21, or TDaP; and A2M increased in rats administered QS-21. Fibrinogen, A2M, and A1AGP increased after LPS administration. Acute phase proteins can be used to monitor inflammatory responses to adjuvants; however, some adjuvants may induce inflammation without higher APPs.
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