Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA

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)

Relative Prenatal and Postnatal Maternal Contributions to Schizophrenia-Related Neurochemical Dysfunction after In Utero Immune Challenge

“…One alternative (but not mutually exclusive) possibility would be that PolyI:C-induced immunological stress during pregnancy may affect the quantity and/or quality of milk production, which is essential for successful postnatal development. On the other hand, it seems unlikely that prenatal PolyI:C exposure could have led to persistent inflammation in the maternal host and cytokines in the milk, because a single administration of PolyI:C is known to result a time-limited elevation of cytokines in the host (Kimura et al, 1994;Fortier et al, 2004b;Meyer et al, 2006b). …”

Evaluation of the In Vitro Pyrogen Test System Based on Proinflammatory Cytokine Release from Human Monocytes: Comparison with a Human Whole Blood Culture Test System and with the Rabbit Pyrogen Test

“…As a representative of such a substance, we examined the activity of poly(I · C), which is a synthetic double-stranded RNA commonly used in fever research as a model of virus infection (16,19). Virus-associated double-stranded RNA is known to be a good cytokine inducer and to be associated with the majority of viral infections; it induces the production of proinflammatory cytokines and substantial amounts of alpha interferon (15). However, the direct action (such as fever) of these cytokines in the influenza virus syndrome is less clear.…”

Acute phase reaction and acute phase proteins

“…TNF-α and IL-1β are induced in response to endotoxin (Dinarello, 1983;Le and Vilcek, 1989;Monshouwer et al, 1996a;1996b;Schindler et al, 1990;Werling et al, 1996). In viral infections, generally the APR is milder (Alsemgeest, 1994;Höfner et al, 1994;Kimura et al, 1995;Nakayama et al, 1993). The main cytokines then released by infected cells are primarily interferons (IFNs), especially IFNγ from mononuclear inflammatory cells, although TNF-α and IL-1β from tissue cells may be involved as well.…”