Subchronic glucocorticoid pretreatment reversibly attenuates IL-beta induced fever in rats; IL-6 mRNA is elevated while IL-1 alpha and IL-1 beta mRNAs are suppressed, in the CNS.
Subchronic (36 h) exposure of rats to corticosterone (CS) (100 mg/pellet,subcutaneously), blocked the pyrogenic response to recombinant human interleukin 113 (rhIL-1 beta, 5 mu g/kg, ip.). CS treatment reduced the basal mRNA levels of IL-1 alpha and IL-1 beta, but elevated the mRNA levels of IL-6 in the hypothalamus and hippocampus as shown by RT-PCR. The CS treatment clamped the cytokine mRNA levels, and injection of rhIL-1 beta to CS treated rats did not significantly affect these altered mRNA levels. IL-6 bioactivity in serum was not significantly changed by CS treatment, but increased 50 times upon injection of rhIL-1 beta. rhIL-1 beta caused a significantly lower induction of serum IL-6 levels in CS pretreated rats (9-fold). The pyrogenic response to injection of rhIL-1 beta has returned 5 days after the removal of the corticosterone pellet, and the hypothalamic cytokine mRNA levels (IL-1 alpha, IL-1 beta and IL-6) have returned to basal. These results suggest that altered and clamped hypothalamic IL-1 alpha, IL-1 beta and IL-6 mRNA levels may be involved in the antipyretic effects of a pretreatment with high doses of CS and that these CS effects are rapidly reversible.
Chai
Z
Z
Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.
Alheim
K
K
Lundkvist
J
J
Gatti
S
S
Bartfai
T
T
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage / Q000627:therapeutic use*; D017931:DNA Primers; D004343:Drug Implants; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000276:immunology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000633:toxicity*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D008297:Male; D016133:Polymerase Chain Reaction; D011749:Pyrogens; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000096:biosynthesis; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000633:toxicity; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D017931:DNA Primers; D004343:Drug Implants; D005938:Glucocorticoids; D007375:Interleukin-1; D015850:Interleukin-6; D011749:Pyrogens; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone