Proinflammatory response and IL-12 expression in HIV-1 infection

HIV-1 infection elicits a broad range of host responses, many of which inte rfere with the regulatory pathways of gene expression of interleukin-12 (IL -12), a heterodimeric cytokine essential for cell-mediated immunity against microbial infection. The inhibition of IL-12 production by accessory cells after HIV-1 infection has been identified as a potential factor responsibl e for impaired innate and Th1 cell-mediated responses observed in AIDS pati ents. The mechanism by which HIV-1 infection suppresses IL-12 gene expressi on is largely uncharacterized. Here we review all pathways identified that could potentially mediate HIV-induced impairment of IL-12 gene expression, such as IL-10, transforming growth factor beta, interferon-alpha/beta, tumo r necrosis factor alpha, Fc receptors, complement regulatory proteins, and receptors, Also discussed is the decreased CD40 ligand induction in CD4 T c ells during HIV infection, which may have a strong impact on T cell-depende nt IL-12 production that is critical for the establishment and maintenance of a Th1 response.