The role of interferon and tumor necrosis factor in the pathogenesis of AIDS.
Cytokines including interferon (IFN) and tumor necrosis factor (TNF) are potent modulators of immune processes. They are synthesized in response to microbial infections and inflammation. TNF and IFN interact with other cytokines to elicit differentiation and cellular responses of specific target cells. In view of their multiple biological effects, we have postulated that dysregulation of IFN and TNF may contribute to the pathogenesis of HIV infection. Here, we review data showing that the expression of IFN-alpha receptors is down-regulated in patients with AIDS. As a consequence, HIV-infected cultured cells and cells from AIDS patients show hyporesponsiveness to IFN action. This could contribute to mechanisms by which HIV evades the antiviral activity of IFN-alpha in HIV-infected cells and raise the question of the usefulness of IFN-alpha in the treatment of end-stage AIDS. TNF is a major mediator of inflammation and sepsis and also is capable of inducing the replication of HIV. TNF synthesis and its receptor expression are upregulated by the acid-labile IFN-alpha subtype present in the sera of HIV-infected individuals. In addition, the acid-labile IFN present in AIDS sera may contribute to the pathophysiological changes in sepsis by rendering the cells from AIDS patients hypersensitive to endotoxin stimulation resulting in further synthesis of TNF. Thus aberrant regulation of these cytokines and their cognate receptors are likely contributing factors to the pathogenesis of AIDS.
Lau
A S
AS
Division of Infectious Diseases, Hospital for Sick Children, Toronto, Ontario, Canada.
Williams
B R
BR
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D007372:Interferons