Production of Interleukin‐4, Interferon (IFN)‐γ and IFN‐α in Human Immunodeficiency Virus‐1 Infection: An Imbalance of Type 1 and Type 2 Cytokines may Reduce the Synthesis of IFN‐α

Abstract

Interferon‐α (IFN‐α) is an important molecule in the antiviral response, but cells from HIV‐1‐infected individuals show a reduced ability to secrete IFN‐α. We investigated an association between an imbalance of type 1/type 2 cytokines and the production of IFN‐α in HIV‐1 infection. We used whole blood culture to study the cytokine production profile, interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4), in response to HIV‐1 antigens and to study the Sendai Virus and HSV‐1‐induced‐production of IFN‐α in seven HIV‐1‐infected patients. An impaired synthesis of IFN‐α was obtained in patients with a predominant IL‐4 production (IL‐4 > IFN‐γ), and we found a positive correlation between the ex vivo production of IFN‐α and the IFN‐γ/IL‐4 ratio but not with the HIV RNA copy number in plasma. We investigated the role of T‐cell‐derived cytokines in the in vitro production of IFN‐α by PBMC from eight healthy donors, activated with Sendai Virus or HSV‐1. Whereas type 2 cytokines (IL‐4, IL‐13) inhibited virus‐induced IFN‐α synthesis, on the contrary, type 1 cytokines (IL‐2, IFN‐γ) enhanced it. A disarray in the T‐cell‐derived cytokine response may play a role in the defect of IFN‐α production in HIV‐1‐infected individuals. Further investigations are needed to explore this hypothesis.

Deciphering the involvement of innate immune factors in the development of the host response to PRRSV vaccination

“…In our studies, a positive correlation between the number of virus-specific IFNG SC present in the peripheral blood of vaccinated pigs and the number of cells capable of releasing IFNA in response to stimulation with PRRSV was observed. This observation is similar to that reported between the ex vivo production of IFNA and IFNG in HIV-1 infected individuals (Hober et al, 1998). This relationship suggests that despite the poor IFNA induction in response to PRRSV, those animals with the highest capacity to produce IFNA when exposed to this virus are also more likely to develop a relatively stronger IFNG response.…”

Atopic Phenotype in Children Is Associated with Decreased Virus-Induced Interferon-α Release

“…So far, we could not identify any specific factors influencing our system, but other studies have described that IL-4 and IL-10 are able to downregulate the release of virus-induced IFN-α [37, 38]. Thus, in the presence of IL-4, bone marrow-derived macrophages of mice were made permissive for virus infection by reducing IFN-α expression [39].…”

IFN-α inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release

“…To add to this complexity, both IL-4 and IL-13 are reported to inhibit IFN-α by PDC. 38 Therefore, basophils and PDC each secrete at least 1 regulatory cytokine that potentially down regulates the cytokine-producing capabilities of the other. Although it has long been suspected that such a control mechanism might exist between basophils and T H 1 lymphocytes, we have yet to find a T H 1-like cytokine possessing inhibitory activity equal to that mediated by IFN-α (JTS, unpublished data).…”