Preliminary report Protective activity of Lentinan in experimental tuberculosis Nadya Markova a, * , Vesselin Kussovski a , Ivanka Drandarska b , Sascha Nikolaeva b , Neli Georgieva a , Tatyana Radoucheva a a Department of Pathogenic Bacteria, Institute of Microbiology, Bulgarian Academy of Sciences, 26 G. Bonchev St., 1113 Sofia, Bulgaria b Department of Immunomorphology, National Centerof Infectious and Parasitic Disease, Yanko Sakazov Boulevard 26, 1113 Sofia, Bulgaria Received 9 December 2002; received in revised form 3 January 2003; accepted 17 June 2003 Abstract Protective effects of Lentinan (Ajinomoto, Japan) against Mycobacterium tuberculosis infection were studied by in vitro and in vivo mouse models. The effectiveness of Lentinan administrated intraperitoneally (i.p.) before infection at a dose of 1 mg/kg three times at 2-day intervals was monitored in vivo by several parameters (body temperature; spleen weight; CFU counts of M. tuberculosis in spleen, liver and lung; and histomorphological observations). Peritoneal macrophages obtained from animals treated with Lentinan were greatly stimulated, as assayed by establishing their number, acid phosphatase activity, H 2 O 2 production and killing ability against M. tuberculosis in vitro. The in vivo model demonstrated that administration of Lentinan before infection can mobilize host defense potential and reduce mycobacterial infection. D 2003 Elsevier B.V. All rights reserved. Keywords: Lentinan; Immunomodulation; Experimental tuberculosis Tuberculosis has become a serious problem and a major health threat worldwide during the recent years. Emergence of multidrug-resistant tuberculosis appears to be a new phenomenon, which sets the pattern for development of new therapeutic strategies [1–3]. Immunotherapy may be considered as alternative treatment to apply in cases with drug-resistant infec- tions [4,5]. It represents an important adjunct to modern chemotherapy of tuberculosis in high-risk patients. Lentinan, a (1-3)-beta-D-glucan isolated from Jap- anese mushroom Lentinus edodes (Shiitake), is a well known immunomodulator. It has been shown to have marked antitumor effects and to enhance the host resistance to bacterial, fungal, viral or parasitic infec- tions [4,6,7]. However, the mechanisms of Lentinan action remain still obscure. Only a limited number of studies concerning immunotherapeutic effects of Len- tinan against tuberculosis are available [5,8]. Because some of the protective effects of Lentinan are medi- ated largely by T helper type 1 (Th1) cells and macrophages, inducing delayed-type sensitivity re- sponse in the host [7–10], of special interest is Lentinan-induced activation of macrophages for the killing of Mycobacterium tuberculosis. Macrophages are the primary cell type involved in the initial uptake of M. tuberculosis and the major effector cells of cell- mediated immunity in tuberculosis [9]. 1567-5769/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/S1567-5769(03)00178-4 * Corresponding author. Tel.: +359-297-93168; fax: +359-989- 2497. E-mail address: semahead@geobiz.net (N. Markova). www.elsevier.com/locate/intimp International Immunopharmacology 3 (2003) 1557 – 1562