The interferon lambda family (IFN-λ1/2/3) is a newly described group of cytokines that are related to both the type-1 interferons and IL-10 family members. These novel cytokines are induced during viral infection and, like type-1 interferons, display significant anti-viral activity. In order to understand their function in more depth, we have examined the ability of IFN-λ1/IL-29 to regulate cytokine production by human immune cells. Whole peripheral blood mononuclear cells (PBMC) exposed to IFN-λ1 specifically upregulated IL-6, -8 and -10 but there were no visible effects on TNF or IL-1. This response was produced in a dose-dependant fashion and was inhibited by IL-10. Examination of purified cell populations isolated from PBMC demonstrated that monocytes, rather than lymphocytes, were the major IFN-λ1-responsive cellular subset, producing IL-6, -8 and -10 in response to IFN-λ1. Monocyte responses induced by low-level LPS stimulation were also synergistically enhanced by the presence of IFN-λ1. Human macrophages were also shown to react to IFN-λ1 similarly to monocytes, by producing the cytokines IL-6, -8 and -10. In conclusion, we have shown that IFN-λ1, a cytokine produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and may therefore be important in activating innate immune responses at the site of viral infection.

In this study we show a significant correlation between a single-nucleotide polymorphism in the 5'-untranslated region of the DEFB1 gene, which probably regulates the gene expression of human beta defensin 1 (hBD-1) and the risk of HIV-1 infection in an Italian paediatric population (97 HIV-1 perinatally infected children), pointing to the importance of innate immunity in HIV-1 infection.

β-Defensins are a family of small cationic peptides involved in the innate response to microbial infection. Although their role in microbial killing is well established, the mechanisms through which this occurs remain largely undefined. Here, using protein array technology, we describe a role for human β-defensins in the induction of an inflammatory cytokine response by human peripheral blood mononuclear cells (PBMCs). Human β-defensins 1, 2, and 3 were examined for induction of an array of cytokines and chemokines. Some cytokines, such as interleukin 8 (IL-8) and monocyte chemoattractant protein 1, were up-regulated by all three defensins, while others, such as IL-6 and IL-10, were induced more selectively. It was notable that each defensin induced a unique pattern of cytokines. This report documents, for the first time, an analysis of the composite cytokine response of human PBMCs to β-defensins. The induction or up-regulation of a number of cytokines involved in the adaptive immune response suggests a possible role for these defensins in linking innate and acquired immunity.