Reduced Adrenal Response and Increased Mortality After Systemic Klebsiella Pneumoniae Infection in interleukin-6-deficient Mice

Eur Cytokine Netw. Oct-Dec 2001;12(4):581-6.


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.

MeSH terms

  • Adrenal Glands / physiopathology*
  • Animals
  • Corticosterone / blood
  • Hypothalamo-Hypophyseal System / physiopathology
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology*
  • Klebsiella pneumoniae / isolation & purification*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / cytology
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / mortality
  • Pneumonia, Bacterial / physiopathology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Corticosterone