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Virus Infections and Sudden Death in Infancy: The Role of Interferon-γ.

Moscovis SM, Gordon AE, Al Madani OM, Gleeson M, Scott RJ, Hall ST, Burns C, Blackwell C - Front Immunol (2015)

Bottom Line: Indigenous Australians had significantly higher proportions of the IFNG T + 874A SNP (TT) associated with high responses of IFN-γ.Active smoking had a suppressive effect on baseline levels of IFN-γ.The results indicate virus infections contribute to dysregulation of cytokine responses to bacterial antigens and studies on physiological effects of genetic factors must include controls for recent or concurrent infection and exposure to cigarette smoke.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute , Newcastle, NSW , Australia ; Hunter Medical Research Institute , New Lambton, NSW , Australia.

ABSTRACT
Respiratory infections have been implicated in sudden infant death syndrome (SIDS). As interferon-γ (IFN-γ) is a major response to virus infection, we examined (1) the frequency of single nucleotide polymorphism (SNP), IFNG T + 874A, in SIDS infants, their parents, and ethnic groups with different incidences of SIDS; (2) model systems with a monocytic cell line (THP-1) and human peripheral blood monocytes (PBMC) for effects of levels of IFN-γ on inflammatory responses to bacterial antigens identified in SIDS; (3) interactions between genetic and environmental factors on IFN-γ responses. IFNG T + 874A genotypes were determined for SIDS infants from three countries; families who had a SIDS death; populations with high (Indigenous Australian), medium (Caucasian), and low (Bangladeshi) SIDS incidences. The effect of IFN-γ on cytokine responses to endotoxin was examined in model systems with THP-1 cells and human PBMC. The IFN-γ responses to endotoxin and toxic shock syndrome toxin (TSST-1) were assessed in relation to genotype, gender, and reported smoking. There was a marginal association with IFNG T + 874A genotype and SIDS (p = 0.06). Indigenous Australians had significantly higher proportions of the IFNG T + 874A SNP (TT) associated with high responses of IFN-γ. THP-1 cells showed a dose dependent effect of IFN-γ on cytokine responses to endotoxin. For PBMC, IFN-γ enhanced interleukin (IL)-1β, IL-6, and tumor necrosis factor-α responses but reduced IL-8 and IL-10 responses. Active smoking had a suppressive effect on baseline levels of IFN-γ. There was no effect of gender or genotype on IFN-γ responses to bacterial antigens tested; however, significant differences were observed between genotypes in relation to smoking. The results indicate virus infections contribute to dysregulation of cytokine responses to bacterial antigens and studies on physiological effects of genetic factors must include controls for recent or concurrent infection and exposure to cigarette smoke.

No MeSH data available.


Related in: MedlinePlus

Effects of IFN-γ, 1 ng ml−1 (IFN 1) or 10 ng ml−1 (IFN 10) on cytokine responses of THP-1 cells to LPS (50 ng ml−1).
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Figure 1: Effects of IFN-γ, 1 ng ml−1 (IFN 1) or 10 ng ml−1 (IFN 10) on cytokine responses of THP-1 cells to LPS (50 ng ml−1).

Mentions: In the preliminary experiments with THP-1 cells, two concentrations of IFN-γ were tested (1 and 10 ng ml−1) to assess the effect of dose on pro-inflammatory responses to LPS. TSST was not assessed in these preliminary studies as previous work indicated that THP-1 cells did not respond to the toxin. IL-6 was not elicited from THP-1 cells in the absence of IFN-γ. The higher concentration of IFN-γ induced significantly higher levels of IL-1β, IL-6, and TNF-α (Figure 1). The anti-inflammatory IL-10 was not detected under any of the conditions tested.


Virus Infections and Sudden Death in Infancy: The Role of Interferon-γ.

Moscovis SM, Gordon AE, Al Madani OM, Gleeson M, Scott RJ, Hall ST, Burns C, Blackwell C - Front Immunol (2015)

Effects of IFN-γ, 1 ng ml−1 (IFN 1) or 10 ng ml−1 (IFN 10) on cytokine responses of THP-1 cells to LPS (50 ng ml−1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356164&req=5

Figure 1: Effects of IFN-γ, 1 ng ml−1 (IFN 1) or 10 ng ml−1 (IFN 10) on cytokine responses of THP-1 cells to LPS (50 ng ml−1).
Mentions: In the preliminary experiments with THP-1 cells, two concentrations of IFN-γ were tested (1 and 10 ng ml−1) to assess the effect of dose on pro-inflammatory responses to LPS. TSST was not assessed in these preliminary studies as previous work indicated that THP-1 cells did not respond to the toxin. IL-6 was not elicited from THP-1 cells in the absence of IFN-γ. The higher concentration of IFN-γ induced significantly higher levels of IL-1β, IL-6, and TNF-α (Figure 1). The anti-inflammatory IL-10 was not detected under any of the conditions tested.

Bottom Line: Indigenous Australians had significantly higher proportions of the IFNG T + 874A SNP (TT) associated with high responses of IFN-γ.Active smoking had a suppressive effect on baseline levels of IFN-γ.The results indicate virus infections contribute to dysregulation of cytokine responses to bacterial antigens and studies on physiological effects of genetic factors must include controls for recent or concurrent infection and exposure to cigarette smoke.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute , Newcastle, NSW , Australia ; Hunter Medical Research Institute , New Lambton, NSW , Australia.

ABSTRACT
Respiratory infections have been implicated in sudden infant death syndrome (SIDS). As interferon-γ (IFN-γ) is a major response to virus infection, we examined (1) the frequency of single nucleotide polymorphism (SNP), IFNG T + 874A, in SIDS infants, their parents, and ethnic groups with different incidences of SIDS; (2) model systems with a monocytic cell line (THP-1) and human peripheral blood monocytes (PBMC) for effects of levels of IFN-γ on inflammatory responses to bacterial antigens identified in SIDS; (3) interactions between genetic and environmental factors on IFN-γ responses. IFNG T + 874A genotypes were determined for SIDS infants from three countries; families who had a SIDS death; populations with high (Indigenous Australian), medium (Caucasian), and low (Bangladeshi) SIDS incidences. The effect of IFN-γ on cytokine responses to endotoxin was examined in model systems with THP-1 cells and human PBMC. The IFN-γ responses to endotoxin and toxic shock syndrome toxin (TSST-1) were assessed in relation to genotype, gender, and reported smoking. There was a marginal association with IFNG T + 874A genotype and SIDS (p = 0.06). Indigenous Australians had significantly higher proportions of the IFNG T + 874A SNP (TT) associated with high responses of IFN-γ. THP-1 cells showed a dose dependent effect of IFN-γ on cytokine responses to endotoxin. For PBMC, IFN-γ enhanced interleukin (IL)-1β, IL-6, and tumor necrosis factor-α responses but reduced IL-8 and IL-10 responses. Active smoking had a suppressive effect on baseline levels of IFN-γ. There was no effect of gender or genotype on IFN-γ responses to bacterial antigens tested; however, significant differences were observed between genotypes in relation to smoking. The results indicate virus infections contribute to dysregulation of cytokine responses to bacterial antigens and studies on physiological effects of genetic factors must include controls for recent or concurrent infection and exposure to cigarette smoke.

No MeSH data available.


Related in: MedlinePlus