IN-VITRO EFFECTS OF SMOKELESS TOBACCO EXTRACT ON TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND INTERLEUKIN-1-BETA (IL-1-BETA) PRODUCTION, ANDON LYMPHOCYTE-PROLIFERATION

The use of smokeless tobacco (moist snuff) products is associated with mucosal lesions, gingival recession, attachment loss, and oral cancer . Despite numerous reports on the general toxic effects of smokeless t obacco extract, little information is available regarding the specific effects of smokeless tobacco on immune response. Inflammatory cytokin es released as a result of smokeless tobacco-induced irritation may pl ay a role in the development of oral mucosal lesions at habitual tobac co placement sites in smokeless tobacco users. Consequently, the purpo se of this study was to determine whether an aqueous extract of smokel ess tobacco (STE) affects the secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin -1 beta (IL-1 beta), and the proliferation o f lymphocytes. A macrophage cell line (J774-A1) was used to measure th e effects of STE on tumor necrosis factor-alpha (TNF-alpha) and interl eukin -1 beta (IL-1 beta) secretion. Mouse splenocytes were used to as sess the effects of STE on lymphocyte proliferation. We found that STE at low concentrations enhanced the production of both TNF-alpha. and IL-1 beta. Furthermore, STE at similar concentrations enhanced mitogen -induced murine splenocyte proliferation. Overall, these data suggest that smokeless tobacco upregulated two key proinflammatory cytokines a nd also induces lymphocyte proliferation. (C) 1998 Elsevier Science Lt d. All rights reserved.