Interferon-Alpha and Tumor Necrosis Factor-Alpha in Serum of Patients in Various Stages of HIV-1 Infection

Sydow, M von; Sönnerborg, Anders; Gaines, Hans; Strannegård, Örjan

doi:10.1089/aid.1991.7.375

Cited by 197 publications

(142 citation statements)

References 30 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Continued IFN-␣͞␤ production during chronic viral infection could be extremely problematic. Serum levels of IFN-␣ are known to be present during various persistent viral infections including human HIV infection (32). Presumably the constant presence of virus induces consistent elevation of IFN-␣͞␤.…”

Section: Discussionmentioning

confidence: 99%

Interferon-α/β inhibition of interleukin 12 and interferon-γ productionin vitroand endogenously during viral infection

Cousens

Orange

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

276

183

View full text Add to dashboard Cite

Interferon ( Interleukin 12 (IL-12) is a heterodimeric cytokine with many functions including induction of interferon (IFN)-␥ by natural killer (NK) cells and generation of T helper 1 (Th1) cells producing IFN-␥ (1). The role of IL-12 in promoting endogenous protective immune responses to viral infections, however, is only beginning to be understood (2, 3). Our studies of IL-12 administration during lymphocytic choriomeningitis virus (LCMV) infections of mice have demonstrated that high concentrations of the factor are detrimental to expansion of protective CD8 ϩ cytotoxic T lymphocytes (CTL) and synergize with endogenous immune responses to promote systemic toxicities (4, 5). These results suggest that, if endogenous IL-12 is to play a role in viral infections requiring CD8 ϩ T cell responses for defense, the levels of expression would have to be tightly regulated. Interestingly, HIV infections are also associated with protective CD8 ϩ CTL (6-9), and cells from HIV-infected individuals are inhibited in their ability to produce IL-12 (10, 11).Studies from this laboratory evaluating endogenous expression and function of IL-12 indicate that the factor is differentially regulated in contrasting viral infections of mice. Although early IL-12 protein expression is induced during murine cytomegalovirus (MCMV) infection (12) and results in NK cell , detectable levels of IL-12 and NK cell IFN-␥ production are not observed during LCMV infection (12). The presence of IL-12 inversely correlates with induction of CTL function; in contrast to MCMV, LCMV infections readily induce high levels of CD8 ϩ CTL activity. In addition, treatments with antibodies neutralizing IL-12 do not significantly modify the prominent late T cell CTL and IFN-␥ responses during LCMV infection (12). These results are in striking contrast to the demonstrated IL-12 dependency of T cell IFN-␥ responses during bacterial and parasitic infections (1-3, 15, 16). Taken together, the studies suggest that IL-12 responses are differentially regulated during particular viral infections, and that IL-12-induced effects under the conditions of viral infections are distinct from those observed during other challenges.One of the conditions distinguishing viral infections is early induction of systemic IFN-␣͞␤ production (17-19). The experiments presented here were undertaken to evaluate the effects of these factors on IL-12 and IFN-␥ expression. The results show that production of the cytokines is inhibited by IFN-␣͞␤. They demonstrate that IFN-␣͞␤ inhibition acts on expression in response to known exogenous inducers of IL-12 and is an endogenous component shaping cytokine expression during viral infections.

show abstract

Section: Discussionmentioning

confidence: 99%

Interferon-α/β inhibition of interleukin 12 and interferon-γ productionin vitroand endogenously during viral infection

Cousens

Orange

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

276

183

View full text Add to dashboard Cite

show abstract

“…The number of circulating pDC is decreased in HIV-1 infection (10), and the lack of IFN-␣ production was suggested to be responsible for HIV-1 disease progression (11,12). In contrast, high plasma titers of IFN-␣ are found during acute HIV-1 infection and reappear during late-stage disease (13). Induction of type I IFNs could be a double-edged sword and might exert pathogenic in addition to protective effects in innate immunity.…”

mentioning

confidence: 99%

HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-α

Hardy

Graham

Shearer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

142

168

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDC) are key players in viral immunity and produce IFN-␣ after HIV-1 exposure, which in turn regulates TNF-related apoptosis-inducing ligand (TRAIL) expression by CD4 ؉ T cells. We show here that infectious and noninfectious HIV-1 virions induce activation of pDC into TRAIL-expressing IFN-producing killer pDC (IKpDC). IKpDC expressed high levels of activation markers (HLA-DR, CD80, CD83, and CD86) and the migration marker CCR7. Surprisingly, CXCR4 and CCR5 were down-regulated on IKpDC. We also show that HIV-1-induced IKpDC depended on Toll-like receptor 7 (TLR7) activation. HIV-1 or TLR7 agonistexposed IKpDC induced apoptosis of the CD4 ؉ T cell line SupT1 via the TRAIL pathway. Furthermore, IFN-␣ produced after HIV-induced TLR7 stimulation was responsible for TRAIL expression and the down-regulation of both CXCR4 and CCR5 by IKpDC. In contrast, activation and migration markers were not regulated by IFN-␣. Finally, IFN-␣ increased the survival of IKpDC. We characterized a subset of pDC with a killer activity that is activated by endosomal-associated viral RNA and not by infection.apoptosis ͉ endocytosis ͉ AT-2 HIV-1 ͉ CCR5 ͉ CXCR4

show abstract

“…Il can also nol be excluded ihat the Ethiopian HIV-I strains may induce IFN-a production poorly. In an earlier study, a correlation was found between the occurrence of IFN-a and HIV-I p24 antigen in Swedish serum samples [20]. Free or complexcd p24 antigen is found only rarely in sera of Ethiopian…”

Section: Discussionmentioning

confidence: 85%

“…Serum levels of TNF-a were determined by an immunoradiometric assay (TNF-alpha IRMA, Medgenix Diagnostics, Brussels, Belgium), as described elsewhere [20). TNF-a values were determined by using a standard curve.…”

Section: Assay Of Tnf-amentioning

confidence: 99%

See 1 more Smart Citation

Raised levels of tumour necrosis factor-alpha and neopterin, but not interferon-alpha, in serum of HIV-1-infected patients from Ethiopia

Ayehunie

Sönnerborg²,

Yemane-Berhan

et al. 1993

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARY Serum levels of tumour necrosis factor‐alpha (TNF‐α). neopterin and interferon‐alpha (IFN‐α) were determined by immunoradiometric assays in 60 HIV‐1+and 20 HIV‐1− subjects from Ethiopia. Swedish samples were used as reference material. The Ethiopian HIV‐1‘ subjects were found to have significantly increased TNF‐α and neopterin, but not IFN‐α levels. Increased levels of TNF‐α and neopterin were frequently found in Ethiopian asymptomatic subjects (37% and 41%). and the concentration increased in patients with AIDS (83% and 90% respectively). The levels of the two substances and the proportion of patients with higher TNF‐α values were lower in the corresponding Swedish subjects. The proportion of sera with raised levels of I FN‐α was very low (asymptomatic 4%, and AIDS 7%) in Ethiopian subjects. These results suggest a very early increase in the TNF‐α production and activation of the cellular immune response, and a low level of IFN‐α synthesis in the natural course of HIV infection in Ethiopia. The aberrations may contribute to a rapid progress of immunodeficiency and cachexia often seen in Ethiopian patients.

show abstract

Interferon-Alpha and Tumor Necrosis Factor-Alpha in Serum of Patients in Various Stages of HIV-1 Infection

Cited by 197 publications

References 30 publications

Interferon-α/β inhibition of interleukin 12 and interferon-γ productionin vitroand endogenously during viral infection

Interferon-α/β inhibition of interleukin 12 and interferon-γ productionin vitroand endogenously during viral infection

HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-α

Raised levels of tumour necrosis factor-alpha and neopterin, but not interferon-alpha, in serum of HIV-1-infected patients from Ethiopia

Contact Info

Product

Resources

About