Age-dependent differences of interleukin-6 activity in cardiac function after burn complicated by sepsis.
Interleukin (IL)-6 is a pleiotropic cytokine that is activated after acute injuries, and plays an important role during aging. We aim to define the role of IL-6 on myocardial dysfunction following a 40% total body surface area burn followed by late (7 days) Streptococcus pneumoniae sepsis (burn plus sepsis) in 2- and 14-month-old wild type and IL-6(-/-) mice. We measured global hemodynamic and cardiac contractile function with left ventricular pressure-volume analysis 24h after sepsis induction, and measured phosphorylated signal transducer and activator of transcription 3 (p-STAT-3), tumor necrosis factor (TNF)-alpha, and IL-1beta in the heart with Western blot analysis. We also measured mRNA expression of IL-6, TNF-alpha, and IL-1beta. Sham injured mice did not manifest any appreciable level of p-STAT-3 or functional deficiencies regardless of age or presence of the IL-6 gene. Burn plus sepsis injury was associated with a significant deterioration of global hemodynamic and cardiac contractile function in WT mice in both age groups. This dysfunction was attenuated by IL-6 deficiency at age 2 months, but accentuated at age 14 months. Aging was associated with an increase in mRNA expression of IL-6 (WT mice), TNF-alpha, and IL-1beta (all mice). At age 14 months, IL-6 deficient mice exhibited a greater TNF-alpha mRNA expression than the wild type mice. We conclude aging is associated with changed cytokine gene transcription, and burn plus sepsis injury further intensifies such gene responses. IL-6 deficiency does not abrogate STAT-3 phosphorylation and it may enhance expression of other inflammatory cytokines. The differential effects of IL-6 deficiency on the cardiac function in young and aging mice cannot be explained by cytokine gene expression alone, and require further studies.
Wang
Lin
L
Department of Anesthesiology and Pain Management, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9068, USA.
Quan
Jiexia
J
Johnston
William E
WE
Maass
David L
DL
Horton
Jureta W
JW
Thomas
James A
JA
Tao
Weike
W
D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000818:Animals; D002056:Burns / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006439:Hemodynamics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction; D010766:Phosphorylation; D011008:Pneumococcal Infections / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D018805:Sepsis / Q000150:complications* / Q000276:immunology / Q000503:physiopathology
D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse