Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-10-16
pubmed:abstractText
Interleukin 12 (IL-12) directs the differentiation of undifferentiated T helper (Th0) cells to T helper type 1 (Th1) cells and induces a cell-mediated immune response. To evaluate the effect of IL-12 on the course of influenza A virus infection, BALB/c mice were administered a daily intraperitoneal dose of 1000 ng of IL-12 or saline on days -1 to +4 for a total of six treatments. The treatment generally enhanced Th1-mediated responses. IFNgamma lung concentrations were 1193 +/- 275 pg/100 microl in controls and 3693 +/- 745 pg/100 microl in IL-12-treated mice at day 5. IFNgamma levels were undetectable at day 13 in controls and 1335 +/- 220 pg/100 microl in IL-12-treated mice. Cytokine production was also assessed at the single-cell level for mediastinal lymph nodes. IL-12 treatment increased the number of IL-2- and IFNgamma-producing cells and decreased the number of IL-4- and IL-10-producing cells. IL-12 treatment decreased the anti-influenza antibody response, especially anti-influenza IgG1 antibody resulting in an increased IgG2a/IgG1 ratio. Primary pulmonary CTL activity on day 5 was low for both groups (10% specific lysis). Secondary CTL activity at day 11 was higher for control mice than for IL-12-treated mice on day 11 (44 versus 34%), but not on day 13. Despite this overall enhancement of Th1-mediated immune functions, the IL-12 treatment increased severity of the disease. Following infection, control and IL-12-treated mice decreased their body weight to approximately 75% of their initial weight. After day 5, the control mice started to recover, while IL-12-treated mice did not begin recovering until day 9. Pulmonary viral titers were 1.6 +/- 0.3 TCID50 in controls at day 5 compared to 2.4 +/- 0.3 for IL-12-treated mice (P < 0.01). In addition, control mice had significantly less severe inflammation and damage on histologic examination. Serum TNFalpha concentrations, undetectable in control mice, were elevated by IL-12 treatment up to 80 pg/ml at day 5 and decreased to zero at day 13. It is concluded that IL-12 administration to influenza-infected mice induces a switch from a Th2- to a Th1-mediated response, but inhibits recovery probably through induction of TNFalpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0166-3542
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-30
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9707374-Animals, pubmed-meshheading:9707374-Antibodies, Viral, pubmed-meshheading:9707374-Body Weight, pubmed-meshheading:9707374-Female, pubmed-meshheading:9707374-Immunoglobulin G, pubmed-meshheading:9707374-Inflammation, pubmed-meshheading:9707374-Influenza A virus, pubmed-meshheading:9707374-Interferon-gamma, pubmed-meshheading:9707374-Interleukin-12, pubmed-meshheading:9707374-Interleukins, pubmed-meshheading:9707374-Lung, pubmed-meshheading:9707374-Mice, pubmed-meshheading:9707374-Mice, Inbred BALB C, pubmed-meshheading:9707374-Orthomyxoviridae Infections, pubmed-meshheading:9707374-Recombinant Proteins, pubmed-meshheading:9707374-T-Lymphocytes, Cytotoxic, pubmed-meshheading:9707374-Th1 Cells, pubmed-meshheading:9707374-Tumor Necrosis Factor-alpha, pubmed-meshheading:9707374-Viral Load
pubmed:year
1998
pubmed:articleTitle
Interleukin 12 administration enhances Th1 activity but delays recovery from influenza A virus infection in mice.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Gainesville 32610-0275, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't