Involvement of the acute phase protein α1-acid glycoprotein in nonspecific resistance to a lethal Gram-negative infection

Abstract

Resistance to Gram-negative infection can be induced by pretreating animals with several agents such as turpentine and interleukin (IL)-1. Because these agents are powerful inducers of acute phase proteins, we wondered whether these proteins, more particularly α1-acid glycoprotein (α1-AGP), are involved in nonspecific resistance to infection. Turpentine and IL-1 protect completely against a lethal challenge of Klebsiella pneumoniae when given 48 and 12-48 h before the challenge, respectively, α1-AGP induction in the serum reached peak values 48 h after turpentine and 12-48 h after IL-1 injection. Administration of α1-AGP, 2 h before a challenge of K. pneumoniae, significantly increased the survival. Numbers of bacteria cultured from blood and organs were significantly lower in mice pretreated with a protective dose of turpentine, IL-1, or α1-AGP. These data suggest that α1-AGP is a possible mediator in turpentine- or IL-1- induced protection because time points of maximal induction of α1-AGP by turpentine or IL-1 and of optimal protection by α1-AGP coincide. Transgenic overexpression of rat α1-AGP protected mice from a K. pneumoniae infection. Bacterial counts in blood and organs were significantly lower in transgenic mice, and only in control mice were large necrotic areas, apoptosis, and blood clots observed in the spleen. Our data suggest that α1-AGP prevents Gram-negative infections and may be an essential component in nonspecific resistance to infection.