Effects of the Th1 and Th2 stimulatory cytokines interleukin-12 and interleukin-4 on human immunodeficiency virus replication
| Autor: | Michael Baseler, MW Saville, Robert Yarchoan, Andrea Foli |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_treatment
Immunology HIV Core Protein p24 Biology Lymphocyte Activation Virus Replication Biochemistry Peripheral blood mononuclear cell Monocytes Cytopathogenic Effect Viral medicine Humans Phytohemagglutinins Interleukin 4 Immunodeficiency Cells Cultured Zalcitabine Monocyte Interleukins Macrophages Antibodies Monoclonal Cell Biology Hematology T-Lymphocytes Helper-Inducer medicine.disease Virology Interleukin-12 Didanosine medicine.anatomical_structure Cytokine HIV p24 Antigen Interleukin 12 HIV-1 Leukocytes Mononuclear Tumor necrosis factor alpha Interleukin-4 Zidovudine Muromonab-CD3 |
| Zdroj: | Blood. 85(8) |
| ISSN: | 0006-4971 |
| Popis: | The cytokines interleukin-12 (IL-12) and IL-4 play important roles in the development of Th1-like (type-1) and Th2-like (type-2) T-cell responses, respectively, and there is evidence that type-1/type-2 T helper imbalances are important in the pathogenesis of human immunodeficiency virus (HIV) disease. With this background, we examined the effects of these cytokines on HIV replication. Neither stimulated HIV replication in fresh peripheral blood mononuclear cells (PBMC). However, in prestimulated PBMC, IL-12, and to a greater extent, IL-4 as well as IL-2, induced production of HIV p24 antigen over 7 days of culture (no cytokine 3,900 x/divided by 1.31 [GM x/divided by SEM] pg/mL; IL-12, 34,300 x/divided by 1.39 pg/mL; IL-4, 283,000 x/divided by 1.14 pg/mL; and IL-2, 328,000 x/divided by 1.31 pg/mL). Neither IL-12- nor IL-4-induced HIV replication was attributable to induction of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, or TNF-beta. Both IL-12- and IL-4-induced HIV replication was associated with selective loss of the CD4+ subset in stimulated cultures. IL-4 stimulated HIV replication in monocyte/macrophages, while IL-12 had little or no effect in these cells. Finally, HIV replication stimulated by IL-12 or IL-4 was inhibited by dideoxynucleosides. Thus, IL-12 and IL-4 enhance HIV replication and HIV-induced cell death in prestimulated PBMC. Through killing of the CD4+ T cells stimulated by these cytokines, this may result in inappropriate type-1/type-2 responses in HIV-infected patients and contribute to their Th1 immunodeficiency. |
| Databáze: | OpenAIRE |
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