Interleukin 18 and interleukin 1beta production is decreased in HIV type 1-seropositive hemophiliacs but not in HIV type 1-seropositive nonhemophiliacs.
In Japan, the proportion of hemophiliacs infected with human immunodeficiency virus type 1 (HIV-1) is 40%, whereas more than 90% are infected with hepatitis C virus (HCV). To evaluate the immunological status of hemophiliacs infected with HIV-1, we investigated the pattern of cytokine production in peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive and -seronegative hemophiliacs, HIV-1-seropositive non-hemophiliacs, and healthy individuals. The production of IL-18 and IL-1beta from PBMCs stimulated with Staphylococcus aureus Cowan strain 1 (SAC) in the HIV-1-seropositive hemophiliacs was significantly decreased in comparison with the other groups. On the other hand, IL-12 production in both HIV-1-seropositive groups was significantly lower than in HIV-1-seronegative groups. TNF-alpha and IL-6 production was similar among the four groups. In contrast, plasma levels of TGF-beta1 were increased in HIV-1-seropositive hemophiliacs, HIV-1-seropositive nonhemophiliacs, and HIV-1-seronegative hemophiliacs, with the highest levels being in HIV-1-seropositive hemophiliacs, suggesting that coinfection with HIV-1 and HCV increases the level of plasma TGF-beta in HIV-1-seropositive hemophiliacs. Treatment of PBMCs from healthy individuals with TGF-beta1 inhibited IL-18 and IL-1beta production without affecting IL-6, IL-10, or TNF-alpha production. Suppression of the expression of caspase 1 mRNA, which is known to be an IL-1beta-converting enzyme and which also cleaves the precursor of IL-18, was observed in the SAC-stimulated PBMCs from healthy individuals after treatment with TGF-beta1 and in the SAC-stimulated PBMCs from HIV-1-seropositive hemophiliacs, suggesting that the decreased production of IL-18 and IL-1beta in HIV-1-seropositive hemophiliacs may be related to the downregulation of caspase 1 mRNA induced by high levels of TGF-beta1 in plasma.
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L
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Department of Microbiology, Yamanashi Medical University, Japan.
Terunuma
H
H
Hanabusa
H
H
Iwamoto
A
A
Oka
S
S
Tanabe
F
F
Chiba
N
N
Kurimoto
M
M
Ikeda
M
M
Okamura
H
H
Dai
J
J
Iwatani
Y
Y
Ishida
T
T
Ito
M
M
D000293:Adolescent; D000328:Adult; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood
D016207:Cytokines; D007375:Interleukin-1; D020382:Interleukin-18; D016212:Transforming Growth Factor beta; D020170:Caspase 1