title: IL-15 Superagonist Expands mCD8+ T, NK and NKT Cells after Burn Injury but Fails to Improve Outcome during Burn Wound Infection.
abstract: BACKGROUND
  Severely burned patients are highly susceptible to opportunistic infections and sepsis, owing to the loss of the protective skin barrier and immunological dysfunction. Interleukin-15 (IL-15) belongs to the IL-2 family of common gamma chain cytokines and stimulates the proliferation and activation of T (specifically memory CD8), NK and NKT cells. It has been shown to preserve T cell function and improve survival during cecal ligation and puncture (CLP)-induced sepsis in mice. However, the therapeutic efficacy of IL-15 or IL-15 superagonist (SA) during infection after burn injury has not been evaluated. Moreover, very few, if any, studies have examined, in detail, the effect of burn injury and infection on the adaptive immune system. Thus, we examined the effect of burn and sepsis on adaptive immune cell populations and the effect of IL-15 SA treatment on the host response to infection.
  
  
  METHODS
  Mice were subjected to a 35% total body surface area burn, followed by wound infection with Pseudomonas aeruginosa. In some experiments, IL-15 SA was administered after burn injury, but before infection. Leukocytes in spleen, liver and peritoneal cavity were characterized using flow cytometry. Bacterial clearance, organ injury and survival were also assessed.
  
  
  RESULTS
  Burn wound infection led to a significant decline in total white blood cell and lymphocyte counts and induced organ injury and sepsis. Burn injury caused decline in CD4+ and CD8+ T cells in the spleen, which was worsened by infection. IL-15 treatment inhibited this decline and significantly increased cell numbers and activation, as determined by CD69 expression, of CD4+, CD8+, B, NK and NKT cells in the spleen and liver after burn injury. However, IL-15 SA treatment failed to prevent burn wound sepsis-induced loss of CD4+, CD8+, B, NK and NKT cells and failed to improve bacterial clearance and survival.
  
  
  CONCLUSIONS
  Cutaneous burn injury and infection cause significant adaptive immune dysfunction. IL-15 SA does not augment host resistance to burn wound sepsis in mice despite inducing proliferation and activation of lymphocyte subsets.
authors: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors: Naeem K
authors: NK
authors: Patil
authors: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors: Liming
authors: L
authors: Luan
authors: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors: Julia K
authors: JK
authors: Bohannon
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors: Yin
authors: Y
authors: Guo
authors: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors: Antonio
authors: A
authors: Hernandez
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors: Benjamin
authors: B
authors: Fensterheim
authors: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.|Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors: Edward R
authors: ER
authors: Sherwood
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002056:Burns / Q000150:complications / Q000276:immunology* / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D019409:Interleukin-15 / Q000819:agonists*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055611:Natural Killer T-Cells / Q000276:immunology / Q000473:pathology; D011552:Pseudomonas Infections / Q000209:etiology / Q000276:immunology / Q000628:therapy; D011550:Pseudomonas aeruginosa; D053647:Receptors, Interleukin-15 / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014946:Wound Infection / Q000209:etiology / Q000276:immunology* / Q000628:therapy
chemical_list: D016207:Cytokines; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D011993:Recombinant Fusion Proteins