A crucial role for IL-6 in the CNS of rats during fever induced by the injection of live E. coli.

Abstract

Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 have been established as important mediators of fever induced by lipopolysaccharide (LPS) from Gram-negative bacteria. Whether these pro-inflammatory cytokines are also important in mediating fever induced by live bacteria remains less certain. We therefore investigated the following: (1) the synthesis of TNF-α, IL-1β, and IL-6 during E. coli-induced fever and (2) the effect of blocking the action of cytokines within the brain on E. coli-induced fever. Body or tail skin temperature (bT or Tsk, respectively) was measured by biotelemetry or telethermometry, every 30 min, during 6 or 24 h. Depending on the number of colony-forming units (CFU) injected i.p., administration of E. coli induced a long-lasting increase in bT of male Wistar rats. The duration of fever did not correlate with the number of CFU found in peritoneal cavity or blood. Because 2.5 × 10(8) CFU induced a sustained fever without inducing a state of sepsis/severe infection, this dose was used in subsequent experiments. The E. coli-induced increase in bT was preceded by a decrease in Tsk, reflecting a thermoregulatory response. TNF-α, IL-1β, and IL-6 were detected at 3 h in serum of animals injected i.p. with E. coli. In the peritoneal exudates, TNF-α, IL-1β, and IL-6 were detected at 0.5 and 3 h after E. coli administration. Moreover, both IL-1β and IL-6, but not TNF-α, were found in the cerebrospinal fluid (CSF) and hypothalamus of animals injected with E. coli. Although pre-treatment (i.c.v., 2 μl, 15 min before) with anti-IL-6 antibody (anti-IL-6, 5 μg) reduced E. coli-induced fever, pre-treatment with either IL-1 receptor antagonist (IL-1ra, 200 μg) or soluble TNF receptor I (sTNFRI, 500 ng) had no effect on the fever response. In conclusion, replicating E. coli promotes an integrated thermoregulatory response in which the central action of IL-6, but not IL-1 and TNF, appears to be important.

• Authors: Denis M Soares, Maria José Figueiredo, Juliano Manvailer Martins, Renes Resende Machado, Carlos Sorgi, Lucia Helena Faciolli, José C Alves-Filho, Fernando Q Cunha, Glória E P Souza
• Journal: Medical microbiology and immunology (Med Microbiol Immunol) Vol. 201 Issue 1 Pg. 47-60 (Feb 2012) ISSN: 1432-1831 [Electronic] Germany
• PMID: 21643979 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Interleukin-1
• Interleukin-1beta
• Interleukin-6
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Body Temperature
• Cerebrospinal Fluid (immunology)
• Cytokines (immunology, metabolism)
• Escherichia coli (immunology, pathogenicity)
• Escherichia coli Infections (immunology, microbiology, mortality, physiopathology)
• Fever (immunology, microbiology, mortality)
• Hypothalamus (immunology)
• Interleukin-1 (immunology, metabolism)
• Interleukin-1beta (immunology, metabolism)
• Interleukin-6 (immunology, metabolism)
• Male
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (immunology, metabolism)