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Changes in hepatic mRNA levels of acute phase proteins during rat adjuvant arthritis
Abstract:
Using specific cDNA probes, we have investigated changes in hepatic mRNA concentrations of the major acute phase proteins fibrinogen, alpha 2-macroglobulin (alpha 2-MG), albumin and alpha 1-acid glycoprotein (alpha 1-AGP) during developing adjuvant arthritis in Lewis rats. Continuously increasing levels in the mRNA of the positive reactants beta-fibrinogen, alpha 2-MG and alpha 1-AGP were found during developing disease with peak levels from day 15 to 21, whereas mRNA concentrations of the negative reactant albumin decreased, reaching their lowest levels on day 11 to 15. As early as 4 days after arthritis induction, the hepatic mRNA levels of beta-fibrinogen, alpha 1-AGP and albumin were distinctly different from control values. The most dramatic changes in the hepatic mRNA levels and plasma concentrations of acute phase reactants were seen between days 11 and 21. These results indicate that overproduction of the major inflammatory cytokines IL-1, TNF-alpha and IL-6, which are now felt to be largely responsible for the acute phase response in the rat, is an early event during adjuvant arthritis and that the highest amounts are produced during the inflammatory phase of the disease. mRNA changes in the acute phase proteins alpha 1-AGP and albumin, which are mainly regulated by IL-1/TNF alpha, were more pronounced than those of alpha 2-MG and beta-fibrinogen, which are predominantly controlled by IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study tracked acute phase protein mRNA in rats with developing arthritis. Key inflammatory proteins increased, while albumin decreased, indicating early cytokine involvement in the inflammatory response.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- The acute phase response is a complex systemic reaction to inflammation.
- Cytokines like IL-1, TNF-alpha, and IL-6 are central mediators of the acute phase response.
Purpose of the Study:
- To investigate changes in hepatic mRNA concentrations of major acute phase proteins during adjuvant arthritis development in Lewis rats.
- To correlate these changes with the inflammatory cytokine milieu.
Main Methods:
- Utilized specific cDNA probes to quantify hepatic mRNA levels of fibrinogen, alpha 2-macroglobulin (alpha 2-MG), albumin, and alpha 1-acid glycoprotein (alpha 1-AGP).
- Monitored these changes throughout the development of adjuvant arthritis in Lewis rats.
Main Results:
- Positive acute phase reactants (beta-fibrinogen, alpha 2-MG, alpha 1-AGP) showed increasing mRNA levels, peaking between days 15-21.
- The negative acute phase reactant albumin exhibited decreased mRNA levels, reaching lowest points on days 11-15.
- Significant deviations from control values were observed as early as day 4 post-induction.
- The most pronounced changes in mRNA and plasma concentrations occurred between days 11 and 21.
Conclusions:
- Overproduction of IL-1, TNF-alpha, and IL-6 is an early event in adjuvant arthritis, driving the acute phase response.
- mRNA changes for alpha 1-AGP and albumin (IL-1/TNF-alpha regulated) were more pronounced than for alpha 2-MG and beta-fibrinogen (IL-6 regulated).