This study investigated the involvement of
prostaglandins and regulated on activation, normal T cell expressed and secreted (
RANTES), in
fever induced by live Staphylococcus aureus (no. 25923, American Type Culture Collection) injection in rats. S. aureus was injected intraperitoneally
at 10(9), 10(10), and 2 × 10(10) colony-forming units (CFU)/cavity, and body temperature (T(b)) was measured by radiotelemetry. The lowest dose of S. aureus induced a modest transient increase in T(b), whereas the two higher doses promoted similar long-lasting and sustained T(b) increases. Thus, the 10(10) CFU/cavity dose was chosen for the remaining experiments. The T(b) increase induced by S. aureus was accompanied by significant decreases in tail skin temperature and increases in
PGE(2) levels in the cerebrospinal fluid (CSF) and hypothalamus but not in the venous plasma.
Celecoxib (selective
cyclooxygenase-2 inhibitor, 2.5 mg/kg po) inhibited the
fever and the increases in
PGE(2) concentration in the CSF and hypothalamus induced by S. aureus.
Dipyrone (120 mg/kg ip) reduced the
fever from 2.5 to 4 h and the
PGE(2) increase in the CSF but not in the hypothalamus. S. aureus increased
RANTES in the peritoneal exudate but not in the CSF or hypothalamus.
Met-RANTES (100 μg/kg iv), a
chemokine (C-C motif) receptor (CCR)1/CCR5 antagonist, reduced the first 6 h of
fever induced by S. aureus. This study suggests that peripheral (local)
RANTES and central
PGE(2) production are key events in the febrile response to live S. aureus injection. As
dipyrone does not reduce
PGE(2) synthesis in the hypothalamus, it is plausible that S. aureus induces
fever, in part, via a
dipyrone-sensitive PGE(2)-independent pathway.