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 alpha(1)-acid glycoprotein (alpha(1)-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. alpha(1)-AGP induction in the serum reached peak values 48 h after turpentine and 12-48 h after IL-1 injection. Administration of alpha(1)-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 alpha(1)-AGP. These data suggest that alpha(1)-AGP is a possible mediator in turpentine- or IL-1-induced protection because time points of maximal induction of alpha(1)-AGP by turpentine or IL-1 and of optimal protection by alpha(1)-AGP coincide. Transgenic overexpression of rat alpha(1)-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 alpha(1)-AGP prevents gram-negative infections and may be an essential component in nonspecific resistance to infection.
Highlights
Resistance to Gram-negative infection can be induced by pretreating animals with several agents such as turpentine and interleukin (IL)-1
Several investigators found that IL-1 plays a crucial role in inducing nonspecific resistance to infection because it can protect mice against a lethal challenge of Pseudomonas aeruginosa, Listeria monocytogenes, C. albicans, and K. pneumoniae [7,8,9,10, 44]
It was shown that pretreatment with IL-6 or tumor necrosis factor (TNF) could protect against a lethal bacterial challenge, these
Summary
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 ␣1-acid glycoprotein (␣1-AGP), are involved in nonspecific resistance to infection. Numbers of bacteria cultured from blood and organs were significantly lower in mice pretreated with a protective dose of turpentine, IL-1, or ␣1-AGP. We studied the possible protection by turpentine oil and IL-1, two well known and very strong inducers of the acute phase response [31,32,33,34], and by ␣1-AGP itself, and we compared the kinetics of induction of ␣1-AGP in the serum and of optimal protection against K. pneumoniae
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