Interleukin-4 causes delayed virus clearance in influenza virus-infected mice

Moran, Thomas M.; Isobe, H; Fernández-Sesma, Ana; Schulman, Jerome L.

doi:10.1128/jvi.70.8.5230-5235.1996

Cited by 132 publications

(64 citation statements)

References 41 publications

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“…In fact, only a few studies have demonstrated IL-4 mediated inhibition of viral replication (Goletti et al, 2002;Lin et al, 2003). Furthermore, expression of IL-4 by recombinant ectromelia virus or vaccinia virus exacerbated infection in vivo and the administration of recombinant IL-4 delayed virus clearance in influenza virusinfected mice (Jackson et al, 2001;Moran et al, 1996;Sharma et al, 1996). In this study, we demonstrate that treatment of Vero E6 cells with IL-4 decreased susceptibility of these cells to SARS-CoV infection by 10-to 100-fold.…”

Section: Discussionmentioning

confidence: 56%

Interferon-γ and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells

2006

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Interferons (IFNs) inhibit severe acute respiratory syndrome coronavirus (SARS-CoV) replication and might be valuable for SARS treatment. In this study, we demonstrate that treatment of Vero E6 cells with interleukin-4 (IL-4) decreased the susceptibility of these cells to SARS-CoV infection. In contrast to IFNs, IL-4 did not show antiviral activity when administered immediately after SARS-CoV infection, suggesting that IL-4 acts early during the SARS-CoV replication cycle. Indeed, binding of recombinant SARS-CoV spike protein to Vero E6 cells was diminished on cells treated with IL-4, but also on cells exposed to IFN-gamma. Consistent with these observations, IL-4 and IFN-gamma downregulated cell surface expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Besides diminished ACE2 cell surface expression, ACE2 mRNA levels were also decreased after treatment with these cytokines. These findings suggest that IL-4 and IFN-gamma inhibit SARS-CoV replication partly through downregulation of ACE2.

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Section: Discussionmentioning

confidence: 56%

Interferon-γ and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells

2006

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“…10 Rather, treatment of mice with IL-4, a Th2 cytokine, resulted in a signi®cant delay in in¯uenza virus clearance. 11 Dysregulation of CD4 + T-cell function is observed with ageing. While decreased production of and response to IL-2 seems to be a common phenomenon in ageing, 5 IFN-c production in the aged was reported to be lower, 30 show no difference, 31 or be higher 6 than in the young.…”

Section: Discussionmentioning

confidence: 99%

“…10 Furthermore, in vivo treatment with IL-4 suppressed the CTL response and IFN-c production, and delayed viral clearance. 11 IL-1b, IL-6 and tumour necrosis factor-a (TNF-a) levels increase in the early stages of in¯uenza infection and are involved in the initiation of the immune response as well as in the in¯ammatory response. IL-6 is involved in T-cell activation and represents an essential competence factor that synergizes with IL-1 to control the initial steps of T-cell activation, including induction of IL-2 and enhancement of responsiveness to IL-2.…”

Section: Introductionmentioning

confidence: 99%

Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus

et al. 2000

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SUMMARYCompared with young mice, old mice infected with in¯uenza virus have signi®cantly higher pulmonary viral titres, although these can be reduced signi®cantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines, especially interferon-c (IFN-c), play an important role in defending against in¯uenza infection. However, there is an age-associated loss of Th1 cytokine production. Prostaglandin E 2 (PGE 2 ) production, which increases with age, can modulate the T helper cell function by suppressing Th1 cytokine production. To investigate the mechanism of vitamin E supplementation on reduction of in¯uenza severity in old mice, we studied the cytokine production by splenocytes, and PGE 2 production by macrophages (Mw), in young and old C57BL mice fed semipuri®ed diets containing 30 (control) or 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and then infected with in¯uenza A/PC/1/73 (H3N2). Old mice fed the control diet had signi®cantly higher viral titres than young mice; old mice fed the vitamin E-supplemented diet had signi®cantly lower pulmonary viral titres than those fed the control diet (P=0 . 02 and 0 . 001 for overall age and diet effect, respectively). Following in¯uenza infection, interleukin (IL)-2 and IFN-c production was signi®cantly lower in old mice than in young mice. Vitamin E supplementation increased production of IL-2 and IFN-c in old mice; higher IFN-c production was associated with lower pulmonary viral titre. Old mice fed the control diet showed signi®cantly higher lipopolysaccharide (LPS)-stimulated Mw PGE 2 production than old mice fed the vitamin E diet or young mice fed either diet. There was no signi®cant age difference in IL-6, IL-1b, or tumour necrosis factor-a (TNF-a) production by splenocytes. Young mice fed the vitamin E-supplemented diet had signi®cantly lower IL-1b (day 7) and TNF-a production (day 5) compared with those fed the control diet. Old mice fed the vitamin E-supplemented diet had signi®cantly lower TNF-a production (day 2) than those fed the control diet. Our results indicate that the vitamin E-induced decrease in in¯uenza viral titre is mediated through enhancement of Th1 cytokines, which may be the result of reduced PGE 2 production caused by vitamin E.

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“…Whereas, Th2 clones are noncytolytic and failed to promote recovery from lethal infection after adoptive transfer (70). Furthermore, in vivo treatment with IL-4 suppressed CTL response and IFN-g production, and delayed viral clearance (71). Only a limited number of studies have investigated the effect of vitamin E on resistance against infections in humans.…”

Section: Vitamin E and Infectionsmentioning

confidence: 99%

Vitamin E and immune response in the aged: molecular mechanisms and clinical implications

Meydani

Han

2005

Immunological Reviews

201

138

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Nutritional status has been indicated as a contributing factor to age-related dysregulation of the immune response. Vitamin E, a lipid-soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed-type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)-2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E(2), a T-cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell-dividing and IL-producing capacities of naive T cells, but not memory T cells. The vitamin E-induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naive T-cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.

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Interleukin-4 causes delayed virus clearance in influenza virus-infected mice

Cited by 132 publications

References 41 publications

Interferon-γ and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells

Interferon-γ and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells

Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus

Vitamin E and immune response in the aged: molecular mechanisms and clinical implications

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