Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1.
Ciliary neurotrophic factor (CNTF) and interleukin-6 (IL-6) potentiate the elevation of serum corticosterone induced by suboptimal doses of interleukin-1 (IL-1). CNTF also potentiates IL-1-induced serum IL-6. Here, we report that four other cytokines (leukemia inhibitory factor [LIF], oncostatin M [OSM], interleukin-11 and cardiotrophin-1) also potentiated the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, all the six cytokines studied induced the acute-phase protein serum amyloid A when administered alone. Because these cytokines differ both in structure and in function, but share gp130 as a subunit of their receptors, these results indicate that signaling through gp130 mediates potentiation of IL-1 activities. The potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. In fact, in IL-6 deficient mice, IL-1 increased serum corticosterone to a level comparable to that observed in wild-type mice. Thus, either endogenous IL-6 does not mediate IL-1-induced corticosterone increase, or its role may be fulfilled by other cytokines. To the extent that gp130-dependent cytokines may serve this role, they may be important feedback regulators of inflammation through the activation of the hypothalamus-pituitary-adrenal axis and the potentiation of acute-phase protein synthesis.
Benigni
F
F
Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Boston, MA, USA.
Fantuzzi
G
G
Sacco
S
S
Sironi
M
M
Pozzi
P
P
Dinarello
C A
CA
Sipe
J D
JD
Poli
V
V
Cappelletti
M
M
Paonessa
G
G
Pennica
D
D
Panayotatos
N
N
Ghezzi
P
P
D000210:Acute-Phase Reaction; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D020934:Ciliary Neurotrophic Factor; D003345:Corticosterone / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D017370:Interleukin-11 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D006131:Growth Inhibitors; C494200:Il6st protein, mouse; D007375:Interleukin-1; D017370:Interleukin-11; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; C092073:cardiotrophin 1; D003345:Corticosterone