Cordycepin is an immunoregulatory active ingredient of Cordyceps sinensis.

We have reported that cordycepin, an adenosine derivative from the fungus Cordyceps, increased interleukin (IL)-10 expression, decreased IL-2 expression and suppressed T lymphocyte activity. In the present study, we further characterized the regulatory effects of cordycepin on human immune cells. Moreover, a traditional Chinese drug, Cordyceps sinensis (CS) that contains cordycepin, was also investigated. Cytometric Bead Array (CBA) was used to determine the concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha and IFN-gamma in culture of peripheral blood mononuclear cells (PBMCs). The results showed that both cordycepin and CS up-regulated IL-10, IL-1beta, IL-6, IL-8 and TNF-alpha; at the same time, they suppressed phytohemagglutinin (PHA)-induced production of IL-2, IL-4, IL-5, IFN-gamma and IL-12. As compared to cordycepin, CS displayed its regulatory effects on IL-2 and IL-10 in a similar dose-dependent manner even with higher efficiency. The binding activity of transcription factors in a human monocytic cell line THP-1 was tested by the trans-AM method, and a higher binding activity of SP1 and SP3 was observed in cordycepin or CS treated cells compared to the control. These results led to the opinion that cordycepin and CS pleiotropically affected the actions of immune cells and cytokine network in a similar fashion. Cordycepin could be an important immunoregulatory active ingredient in Cordyceps sinensis. In addition, CS may contain substances which possess synergism with cordycepin, as CS showed a higher efficiency in the production of IL-10 and IL-2 than cordycepin. However, merits of these effects in pharmacology and clinical medicine have yet to be proven and the precise mechanism of these immune regulatory actions should be researched.

Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we present the initial data of the first seven patients treated at our institution. MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks. RESULTS: After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died. CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.

New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency.

There is growing interest in manipulating adenosine (Ado) signal transduction to control inflammation and autoimmunity. This concept probably originated with the discovery of severe combined immunodeficiency disease (SCID) in infants with inherited deficiency of adenosine deaminase (ADA). However, the basis for immunosuppression by Ado has not been well defined, and effects of 2'-deoxyadenosine (dAdo), which does not activate Ado receptors, have also been implicated in causing SCID. Here I discuss recent evidence that Ado, acting through its A2A receptor, interferes with NF-kappa B activation in antigen-receptor-stimulated B and T lymphocytes. I also assess the relative contributions of Ado and dAdo to the pathogenesis of ADA-deficient SCID.

[Immunological markers of disease activity in the course of 2-CDA treatment of multiple sclerosis]. / Immunologiczne markery aktywnosci choroby w przebiegu leczenia kladrybina stwardnienia rozsianego.

52 clinically definite multiple sclerosis (MS) patients were treated with subcutaneous injection of 5 mg 2-CDA in 5 consecutive days. The injection courses were repeated 6 times in one month interval. The MRI pattern and immunological markers were studied in serum and CSF before and after 6 months of treatment. The obtained results suggest that treatment with 2-CDA has not any significant effect on humoral immunological events in multiple sclerosis, what is in contrast to some normalization of cellular immunopathological processes.