Reduced adrenal response and increased mortality after systemic Klebsiella pneumoniae infection in interleukin-6-deficient mice.
During bacterial infections, both the immune system and the hypothalamus-pituitary-adrenal (HPA) axis are activated. The role of IL-6 in the activation of the HPA axis during bacterial sepsis is not fully understood. The aim of the present study was to investigate the role of endogenous IL-6 in a potentially lethal infection with Klebsiella pneumoniae and the concomitant activation of the HPA axis. We examined the mortality of IL-6-/- and IL-6+/+ mice after intravenous (i.v.) infection with K. pneumoniae as well as the bacterial outgrowth in several organs. Subsequently, the influence of endogenous IL-6 on the effect of i.v. administration of K. pneumoniae on the plasma levels of corticosterone and the pro-inflammatory cytokines TNF-alpha and IL-1alpha was investigated in these mice. The present study demonstrates that IL-6-/- mice are more susceptible than IL-6+/+ mice to a systemic Gram-negative infection with K. pneumoniae, leading to increased outgrowth of microorganisms in the organs of the mice. Moreover, this infection is associated with a reduced adrenal response in IL-6-/- mice. We conclude that IL-6-/- mice are more susceptible to Gram-negative bacterial infections, which is mainly due to an impaired recruitment of granulocytes to the site of infection in the absence of IL-6. Furthermore, the reduced adrenal response may be an explanation for the strong inflammatory response with higher TNF-alpha plasma levels in IL-6-/- mice.
van Enckevort
F H
FH
Department of Endocrinology (531), Nijmegen University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Sweep
C G
CG
Span
P N
PN
Netea
M G
MG
Hermus
A R
AR
Kullberg
B J
BJ
D000311:Adrenal Glands / Q000503:physiopathology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D007711:Klebsiella pneumoniae / Q000302:isolation & purification*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone