AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 6 1596-R1605, Copyright © 1994 by American Physiological Society
Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA
M. Kimura, L. A. Toth, H. Agostini, A. B. Cady, J. A. Majde and J. M. Krueger
Department of Physiology, University of Tennessee, Memphis 38163.
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)
