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Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA
M Kimura1, L A Toth, H Agostini
1Department of Physiology, University of Tennessee, Memphis 38163.
Abstract:
Infection of injury results in several systemic and central reactions termed the acute phase response (APR). Substantial evidence suggests that cytokines induced by microbes initiate the APR. We compared the APR induced in rabbits by a model bacterial stimulus, lipopolysaccharide (LPS), to that induced by a model viral stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C). The cytokine mRNA responses in a mouse macrophage cell line (RAW 264.7) to LPS or poly I:C were also determined. Rabbits were injected intravenously or intracerebroventricularly with different doses of LPS or poly I:C. Colonic temperatures (Tco) and blood samples were taken at the time of injection and at 3, 6, and 24 h after injection. Leukocyte numbers, serum antiviral activity, serum ceruloplasmin, and plasma fibrinogen were analyzed. Both intravenously injected LPS and poly I:C increased Tco, decreased leukocytes, and increased ceruloplasmin. Only LPS by the intravenous route increased fibrinogen, whereas only intravenously injected poly I:C induced antiviral activity. Intracerebroventricular injections of LPS and poly I:C also elicited dose-dependent febrile responses but did not change the hematologic APR significantly except for fibrinogen. The primary distinctions between LPS and poly I:C with respect to cytokine induction in the RAW 264.7 macrophage cell line were that LPS failed to induce interferon (IFN)-alpha, poly I:C induced interleukin (IL)-6 mRNA minimally and for a shorter time period than did LPS, and LPS induced IL-1 alpha and IFN-beta more rapidly than did poly I:C.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Bacterial lipopolysaccharide (LPS) and viral polyriboinosinic:polyribocytidylic acid (poly I:C) trigger distinct acute phase responses (APR) in rabbits, influencing fever, blood counts, and specific protein levels differently.
Area of Science:
- Immunology
- Neuroscience
- Biochemistry
Background:
- Infection and injury trigger the acute phase response (APR), a systemic and central reaction.
- Cytokines, induced by microbes, are known initiators of the APR.
Purpose of the Study:
- To compare the acute phase response (APR) induced by a bacterial stimulus, lipopolysaccharide (LPS), with that induced by a viral stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C).
- To investigate the cytokine mRNA responses in a mouse macrophage cell line (RAW 264.7) to LPS and poly I:C.
Main Methods:
- Rabbits were injected intravenously or intracerebroventricularly with LPS or poly I:C.
- Colonic temperatures, leukocyte counts, serum antiviral activity, ceruloplasmin, and plasma fibrinogen were analyzed.
- Cytokine mRNA expression in RAW 264.7 cells was determined.
Main Results:
- Both LPS and poly I:C increased body temperature and ceruloplasmin, and decreased leukocytes when injected intravenously.
- Intravenous LPS uniquely increased fibrinogen, while intravenous poly I:C uniquely induced antiviral activity.
- Intracerebroventricular injections of both stimuli caused fever but had limited hematologic effects, except for fibrinogen.
- Distinct cytokine mRNA profiles were observed, with LPS failing to induce interferon-alpha, and differential induction of interleukin-6, interleukin-1 alpha, and interferon-beta.
Conclusions:
- LPS and poly I:C elicit differential systemic and central acute phase responses.
- The distinct cytokine induction patterns by LPS and poly I:C contribute to their varied effects on the APR.
- These findings highlight the specific roles of bacterial and viral stimuli in modulating the host's inflammatory and immune responses.