title: Severe lymphopenia is associated with elevated plasma interleukin-15 levels and increased mortality during severe sepsis.
abstract: Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock. At admission, 24 patients (26.1%) had severe lymphopenia, defined as lymphocyte counts of less than 0.5 × 10(3)/μL. Severe lymphopenia was associated with significantly higher plasma levels of tumor necrosis factor α, IL-6, IL-8, and IL-10 and was also independently associated with 28-day mortality (adjusted hazard ratio, 3.532; 95% confidence interval, 1.482-8.416; P = 0.004). The levels of plasma IL-15, but not IL-7, were increased modestly in patients with severe lymphopenia compared with those without (median, 12.2 vs. 6.4 pg/mL; P = 0.005). The elevated plasma IL-15 levels were contrarily associated with significantly decreased B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells. In conclusion, severe lymphopenia was associated with increased mortality in patients with severe sepsis. We found that patients with sepsis with severe lymphopenia had down-regulated B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells, despite increased plasma IL-15 concentrations. Whether IL-7 and IL-15 are insufficient in patients with severe lymphopenia during severe sepsis warrants further investigations.
authors.affiliation: *Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, National Taiwan University College of Medicine, Hsin-Chu, Taiwan; †Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; ‡Department of Internal Medicine and Department of Critical Care Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan; §Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; ∥Department of Epidemiology, Warren Alpert Medical School of Brown University, Rhode Island, USA; and ¶Department of Medical Research, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Kuei-Pin
authors.initials: KP
authors.lastname: Chung
authors.forename: Hou-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Shyh-Chyi
authors.initials: SC
authors.lastname: Lo
authors.forename: Lih-Yu
authors.initials: LY
authors.lastname: Chang
authors.forename: Shu-Yung
authors.initials: SY
authors.lastname: Lin
authors.forename: Aristine
authors.initials: A
authors.lastname: Cheng
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Meng-Rui
authors.initials: MR
authors.lastname: Lee
authors.forename: Yi-Jung
authors.initials: YJ
authors.lastname: Chen
authors.forename: Hsin-Han
authors.initials: HH
authors.lastname: Hou
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Hsu
authors.forename: Jih-Shuin
authors.initials: JS
authors.lastname: Jerng
authors.forename: Chao-Chi
authors.initials: CC
authors.lastname: Ho
authors.forename: Miao-Tzu
authors.initials: MT
authors.lastname: Huang
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005260:Female; D016654:Genes, RAG-1 / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D019409:Interleukin-15 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008231:Lymphopenia / Q000097:blood* / Q000401:mortality*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000401:mortality*
chemical_list: D019409:Interleukin-15; D015850:Interleukin-6; D015851:Interleukin-7; D016209:Interleukin-8; D016753:Interleukin-10