Developmental regulation of the hepatic acute phase response

Area of Science:

• Biochemistry
• Developmental Biology
• Immunology

Background:

• The acute phase response is a critical innate immunity mechanism.
• Ontogenetic regulation of this response in early development is not fully understood.

Purpose of the Study:

• To investigate the ontogenetic regulation of the acute phase response in Fischer rats.
• To analyze the expression of specific hepatic serine protease inhibitor mRNAs during inflammation at different postnatal ages.

Main Methods:

• Induced inflammation in rat litters at various postnatal ages using an unstated method.
• Quantified four homologous rat hepatic serine protease inhibitor (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin) mRNAs in liver tissues 24 hours post-induction.
• Evaluated responses in hypophysectomized animals.

Main Results:

• Animals exhibited both positive and negative acute phase responses, but these were attenuated in younger animals, reaching adult levels between days 7-19.
• Alpha 1-antitrypsin mRNA showed no response; Spi 2.2 mRNA exhibited 50% of the adult response on days 3 and 7.
• Spi 2.1 and Spi 2.3 mRNAs, negative acute phase reactants, demonstrated attenuated responses in infant animals (33% and 40% respectively).
• In hypophysectomized rats, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin responses were similar to normal animals, while Spi 2.1 mRNA did not change.

Conclusions:

• Infant animals display a blunted acute phase response to tissue injury, with multiple factors contributing to the adult response development.
• Pituitary immaturity may be implicated in the suppressed inflammatory response of Spi 2.1 mRNA in infant animals.
• These related genes offer a valuable tool for studying gene expression regulation in inflammation and development.