Interferon-a IFN

Figure 22.2 Cellular activation by CpG DNA. CpG DNA directly activates dendritic cells (DCs), monocytes and macrophages, to express increased levels of co-stimu-latory molecules, to increase antigen presentation, and to secrete high levels of chemokines and cytokines, such as interleukin 12 (IL-12), interferon-a(IFN-a), and tumor necrosis factor-a (TNF-a), and monocytes and macro-phages have increased antibody-dependent cellular cytotoxicity (ADCC) activity. NK cells are induced to express IFN-7 by these cytokines acting in concert with CpG, and have increased lytic activity. B cells rapidly produce IL-b and IL-10 and express increased levels of costimulatory molecules. B cells rapidly enter the cell cycle and become resistant to some forms of activation-induced cell death. T cells are not directly activated by CpG, but because of the T helper 1 (Thl)-like cytokine environment, and the increased antigen presenting cell (APC) activity, antigen-specific Thl cells and cytotoxic T lymphocytes (CTL) are generated.

The role of cytokines, especially interferon-a (IFN-a), was reviewed by Ronnblom and Aim (R12). The relationship of cytokines and SLE was first demonstrated by increasing serum levels of IFN-a in SLE patients (H15, Y7, B5). The evidence that IFN-a plays a role in the pathogenesis of SLE includes (1) the levels of IFN-a are correlated with disease activity (Y7, B5, B11) and (2) IFN-a therapy of patients with nonautoimmune disease frequently results in production of anti-dsDNA antibodies or SLE (R14, Kl, R13, II). 

Interferon-a (IFN-a) Leukocytes B cells proliferation and differentiation NK cells stimulates cytolytic activity Tc cells increases generation APCs increases MHC 1 and II expression Others increases MHC 1 and FcR expression induces antiviral state... 

A. Interferons are a group of cytokines that include interferon-a (IFN-a), interferon-P (IFN-P) and inter-feron-y (IFN-y). The interferons are naturally protective substances. For example, IFN-a and IFN-P are produced in response to viral infection and inhibit viral replication plus assist the induction of viral resistance. Not only do they possess antiviral activity but they also mediate the response to other infectious agents, dem-... 

Imiquimod (Aldara) is a synthetic imidazoquinoline amine believed to exert immunomodulatory effects by acting as a ligand at toll-like receptors in the innate immune system and inducing the cytokines interferon-a (IFN-a), tumor necrosis factor-a (TNF-a), and lL-1, lL-6, lL-8, lL-10, and lL-12. 

During the last 10 years, hepatitis B treatment has made significant progresses. For example, two biologies have been approved by the FDA, namely, interferon-a (IFN-a) and Pegylated-interferon-a (PEG-IFN-a). Also on the market are five small molecule... 

Another Raf kinase inhibitor, sunitinib (Sutent), was approved in 2006 based on a multi-center, international randomized trial enrolling 750 patients with treatment-naive metastatic renal cell carcinoma (Motzer et al. 2007). In that study, patients were randomized to receive either Sutent or interferon-a (IFN-a). Common metastatic sites included lung, lymph nodes, bone, and liver. There were 96 events (25.6%) of progression/death on Sutent compared with 154 events (41.1%) on IFN-a. Median progression-free survival was 47.3 weeks for Sutent-treated patients and 22.0 weeks for patients treated with IFN. Objective response rate on the Sutent arm was 27.5 vs 5.3% on IFN-a arm. 

Most patients with thin local (stage I) melanoma can be cured by local excision and do not require adjuvant therapy. However, melanoma is an extremely aggressive disease with high metastatic potential and a notoriously high resistance to cytotoxic agents. There are several approved postoperative adjuvant therapies for malignant melanoma. Interferon-a (IFN-a) is the most commonly used adjuvant immunotherapy for advanced melanoma. High-dose interleukin-2 (IL-2) has... 

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