Interleukin-12 and host defense against murine Pneumocystis pneumonia.
Little is known about the role of the cytokine interleukin-12 (IL-12) in Pneumocystis pneumonia or its potential use as immunotherapy. We asked whether release of IL-12 is part of the normal host response to this infection and whether local treatment with IL-12 or gene transfer of IL-12 could accelerate clearance of infection. IL-12 was assayed by enzyme-linked immunosorbent assay in normal mice and in mice deficient in IL-12 after inoculation of Pneumocystis carinii. P. carinii-infected mice were treated with local instillation of IL-12 and gene transfer of the IL-12 gene. Inoculation of P. carinii into normal mice evoked a brisk release of IL-12 into lung tissue, and IL-12 P35-deficient mice showed delayed clearance of infection measured by PCR for P. carinii rRNA. In control mice, intranasal recombinant IL-12 accelerated clearance of infection, and this was associated with increased recruitment of inflammatory cells into lavage fluid and increased release of tumor necrosis factor alpha, IL-12, and gamma interferon. Similar results were observed in infected mice depleted of CD4+ lymphocytes by using in vivo transfer of the IL-12 gene in a replication-deficient adenoviral vector. IL-12 is part of the normal host response to infection with P. carinii. IL-12 therapy can enhance host resistance to infection in both normal mice and mice depleted of CD4+ T lymphocytes. A treatment effect of IL-12 is mediated through enhanced inflammatory cell recruitment into lung tissue and increased tissue concentrations of proinflammatory cytokines.
Ruan
Sanbao
S
Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, New Orleans, LA 70112, USA.
McKinley
Laura
L
Zheng
Mingquan
M
Rudner
Xiaowen
X
D'Souza
Alain
A
Kolls
Jay K
JK
Shellito
Judd E
JE
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000032:analysis; D005260:Female; D015316:Genetic Therapy; D007322:Instillation, Drug; D018664:Interleukin-12 / Q000032:analysis / Q000172:deficiency / Q000276:immunology* / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000276:immunology; D016676:Macrophages, Alveolar; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D045363:Pneumocystis carinii / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology*; D012331:RNA, Fungal / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines; D012331:RNA, Fungal; D018664:Interleukin-12